doi.org/10.26434/chemrxiv.12252965.v1

Repurposing Therapeutics to Identify Novel Inhibitors Targeting 2'-O-Ribose Methyltransferase Nsp16 of SARS-CoV-2

Yuanyuan Jiang, Lanxin Liu, Morenci Manning, Madison Bonahoom, Aaron Lotvola, Zeng-Quan Yang

Submitted date: 06/05/2020 • Posted date: 11/05/2020 Licence: CC BY-NC-ND 4.0 Citation information: Jiang, Yuanyuan; Liu, Lanxin; Manning, Morenci; Bonahoom, Madison; Lotvola, Aaron; Yang, Zeng-Quan (2020): Repurposing Therapeutics to Identify Novel Inhibitors Targeting 2'-O-Ribose Methyltransferase Nsp16 of SARS-CoV-2. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12252965.v1

Three coronaviruses (CoVs): severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and the recently identified SARS-CoV-2 in December 2019, have caused deadly pneumonia in humans since the beginning of the 21st century. The SARS-CoV-2 causes coronavirus disease-19 (COVID-19) with influenza-like symptoms ranging from mild discomfort to severe lung injury and multi-organ failure, eventually leading to death. As of April 30, 2020, more than three million (3,175,207) COVID-19 cases were reported worldwide, and more than 220,000 (224,172) patients have died (https://www.who.int/emergencies/diseases/novel-coronavirus-2019). Effective treatments and vaccines for SARS-CoV-2 infection do not currently exist. Thus, it will be of great benefit to identify and repurpose already well-characterized compounds and approved drugs for use in combating COVID-19. CoVs are positive-sense RNA viruses that replicate in the cytoplasm of infected cells. Replication and transcription of the CoV RNA genome are achieved by a complex RNA replication/transcription machinery, consisting of at least 16 viral nonstructural proteins (nsp). Previous studies demonstrated that nsp16 proteins of SARS-CoV-1 and MERS-CoV have methyltransferase (MTase) activities that catalyze methylation of the first transcribed nucleotide at the ribose 2’-O position (2’-O-Me). The 2’-O-Me of virus cap RNAs protects itself from degradation by 5′-3′ exoribonucleases, ensures efficient translation, and helps to prevent recognition by the host innate immune system. The importance of nsp16 2'-O-MTase activity for CoV infection and pathogenesis was previously documented by in vitro and in vivo studies. For SARS-CoV-1, the absence of nsp16 2′-O-MTase activity results in significant attenuation characterized by decreased viral replication, reduced weight loss, and limited breathing dysfunction in mice. In addition, nsp16 down-regulates the activities of innate immune sensing factors: retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 protein (MDA5). Thus, inhibition of nsp16 2’-O-MTase activities should restrain viral replication and enable recognition by the host innate immune system, making the nsp16-MTase a promising target for the identification of new anti-SARS-CoV-2 drugs. In the present study, we employed structural analysis, virtual screening, and systematic drug repurposing approaches to identify “approved” drugs which can act as promising inhibitors against nsp16 2′-O-MTase of SARS-CoV-2. We first performed comparative analysis of primary amino acid sequences and crystal structures of seven human CoVs and defined the key residues for nsp16 2-O’-MTase functions. From the virtual screening against nsp16 2′-O-MTase of SARS-CoV-2, we provide a ranking of the predicted binding affinities of 1,380 top hit compounds corresponding to 967 “approved” drugs. Furthermore, we have calculated various structural parameters of our top-ranking drugs. Our studies provided the foundation to further test and repurpose these candidate drugs experimentally and clinically for COVID-19 treatment.

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NSP16 full manuscript (5-6-2020)_Submitted Version.pdf (8.30 MiB) view on ChemRxiv download file

NSP16- total Sup Fig and tab (5-6-2020).pdf (2.42 MiB) view on ChemRxiv download file Repurposing therapeutics to identify novel inhibitors targeting 2'-O-ribose methyltransferase nsp16 of SARS-CoV-2

Yuanyuan Jiang, Lanxin Liu, Morenci Manning, Madison Bonahoom, Aaron Lotvola and Zeng- Quan Yang

Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA. Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.

Corresponding author: Zeng-Quan Yang, Ph.D., Barbara Ann Karmanos Cancer Institute, 4100 John R Street, HWCRC 815, Detroit, MI 48201 Tel: (313)576-8339; Fax: (313)576-8029; E- mail: [email protected]

Key Word: SARS-CoV-2, nsp16, methyltransferase, virtual screening

Abstract

SARS-CoV-2, an emerging coronavirus, has spread rapidly around the world, resulting in over three million cases and more than 220,000 deaths as of April 30, 2020. Effective treatments and vaccines for SARS-CoV-2 infection do not currently exist. Previous studies demonstrated that nonstructural protein 16 (nsp16) of coronavirus is an S-adenosyl methionine (SAM)-dependent 2’-O-methyltransferase (2’-O-MTase) that has an important role in viral replication and prevents recognition by the host innate immune system. In the present study, we employed structural analysis, virtual screening, and systematic drug repurposing approaches to identify “approved” drugs which can act as promising inhibitors against nsp16 2′-O-MTase of SARS-CoV-2. We provide a ranking of the predicted binding affinities of 1,380 top hit compounds corresponding to 967 drugs. Furthermore, we have calculated various structural parameters of our top-ranking drugs, including Hesperidin and Sonedenoson, which have previously been clinically approved or investigated for treating various other diseases. Our studies provided the foundation to further test and repurpose these candidate drugs experimentally and clinically for COVID-19 treatment.

Introduction

Three coronaviruses (CoVs): severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and the recently identified SARS- CoV-2 in December 2019, have caused deadly pneumonia in humans since the beginning of the 21st century [1-3]. The SARS-CoV-2 causes coronavirus disease-19 (COVID-19) with influenza-like symptoms ranging from mild discomfort to severe lung injury and multi-organ failure, eventually leading to death. As of April 30, 2020, more than three million (3,175,207) COVID-19 cases were reported worldwide, and more than 220,000 (224,172) patients have died (https://www.who.int/emergencies/diseases/novel-coronavirus-2019). Effective treatments and vaccines for SARS-CoV-2 infection do not currently exist. Thus, it will be of great benefit to identify and repurpose already well-characterized compounds and approved drugs for use in combating COVID-19.

CoVs are positive-sense RNA viruses that replicate in the cytoplasm of infected cells. Replication and transcription of the CoV RNA genome are achieved by a complex RNA replication/transcription machinery, consisting of at least 16 viral nonstructural proteins (nsp) [3, 4]. Previous studies demonstrated that nsp16 proteins of SARS-CoV-1 and MERS-CoV have methyltransferase (MTase) activities that catalyze methylation of the first transcribed nucleotide at the ribose 2’-O position (2’-O-Me) [5-7]. The 2’-O-Me of virus cap RNAs protects itself from degradation by 5′-3′ exoribonucleases, ensures efficient translation, and helps to prevent recognition by the host innate immune system [8]. The importance of nsp16 2'-O-MTase activity for CoV infection and pathogenesis was previously documented by in vitro and in vivo studies [8-11]. For SARS-CoV-1, the absence of nsp16 2′-O-MTase activity results in significant attenuation characterized by decreased viral replication, reduced weight loss, and limited breathing dysfunction in mice [12]. In addition, nsp16 down-regulates the activities of innate immune sensing factors: retinoic acid-inducible gene I (RIG-I) and melanoma differentiation- associated gene 5 protein (MDA5) [12, 13]. Thus, inhibition of nsp16 2’-O-MTase activities should restrain viral replication and enable recognition by the host innate immune system, making the nsp16-MTase a promising target for the identification of new anti-SARS-CoV-2 drugs.

In the present study, we employed structural analysis, virtual screening, and systematic drug repurposing approaches to identify “approved” drugs which can act as promising inhibitors against nsp16 2′-O-MTase of SARS-CoV-2. We first performed comparative analysis of primary amino acid sequences and crystal structures of seven human CoVs and defined the key residues for nsp16 2-O’-MTase functions. From the virtual screening against nsp16 2′-O-MTase of SARS-CoV-2, we provide a ranking of the predicted binding affinities of 1,380 top hit compounds corresponding to 967 “approved” drugs. Furthermore, we have calculated various structural parameters of our top-ranking drugs. Our studies provided the foundation to further test and repurpose these candidate drugs experimentally and clinically for COVID-19 treatment.

Results

Comparative sequence and structure analysis of nsp16 2’-O-MTases

To identify inhibitors targeting nsp16, we first performed comparative analysis of primary amino acid sequences and crystal structures of seven human CoVs. Supplementary Table 1 lists the detailed genome and protein information that were employed in this study. In primary amino acid sequences, nsp16 of SARS-CoV-2 was found to be 93.3% identical to SARS-CoV-1, but only 56.6 – 65.9% identical to five other human CoVs, including MERS-CoV, and four least harmful HCoV-OC43, -HKU1, -NL63, and -229E. The nsp16 proteins belong to a class of S- adenosyl methionine (SAM)-dependent 2’-O-MTases present in all life forms, and they all contain the conserved catalytic KDKE motif (K46, D130, K170, and E203 in SARS-CoV-2) (Figure 1A & B) [5, 6, 14]. Previous studies in SARS-CoV-1 demonstrated that the 2’-O-MTase activity is completely abolished by single mutation of any residue in this KDKE motif [14].

We next analyzed crystal structures of nsp16s obtained from SARS-CoV-2, SARS-CoV-1, and MERS-CoV that are available in RCSB Protein Data Bank (PDB) (Supplementary Table S1) [5, 6, 15]. The three-dimensional (3D) structures of nsp16s were solved in complex with nsp10 that functions as a stimulatory factor to regulate 2’-O-MTase function (Supplementary Figure S1) [5, 6, 15]. Structural alignment was performed using TM-align, an algorithm for sequence- independent protein structure comparisons [16]. We revealed the highest coverage, percent identity, and structural conservation between SARS-CoV-2 and SARS-CoV-1 nsp16 bound to SAM [PDB: 6W4H: chain A (Resolution: 1.80 Å); and 3R24: chain A (Resolution: 2.00 Å), respectively], with TM-score 0.958 and Root Mean Square Deviation (RMSD) =0.89. The SARS-CoV-2 nsp16 structure is also highly similar to the MERS-CoV complex bound to SAM and a cap analogue: 7-methyl-GpppA [PDB:5YNM: chain A (Resolution: 1.68 Å)], with TM- score 0.956 and RSMD=0.80 (Supplementary Figure S2). Since no structures with cap analogue or substrate RNA are available for SARS-CoV-1 and -2 nsp16 currently, the RNA binding pocket and key residues for RNA recognition were generated by the superposition of 6W4H and 5YNM. As shown in Figure 1C & D, the conserved KDKE catalytic tetrad motif is located at the bottom of the RNA binding pocket. The KDKE might bind the first adenine nucleotide, conserved in SARS genomic and subgenomic RNAs, as the acceptor of the methyl group during methylation. Notably, previous structural and biochemical studies revealed that the nsp16 2′-O- MTase activity of SARS-CoV-1 is sequence-dependent as it could only methylate m7GpppA- capped RNA, where the first nucleotide is absolutely restricted to adenosine [5, 6, 14]. Other residues including K38, Y47, Y181, and D133 are also involved in the RNA binding. Structural analysis also revealed that residues N43, Y47, G71, A72, S74, G81, D99, L100, N101, D114, and M131 coordinate SAM substrate binding in both SARS-CoV-1 and -2 through hydrogen bonds and water-mediated interactions [7].

In humans, cap methyltransferase 1 (CMTR1) is a specific 2′-O-MTase that catalyzes Cap1 methylation of mRNA [17, 18]. We also performed comparative analysis of the crystal structures of CoV-2 nsp16 and human 2’-O-MTase CMTR1. SARS-CoV-2 nsp16 and human CMTR1 MTase domain share little primary amino acid sequence identity (12.1%) based on the Pairwise Sequence Alignment with the Needleman-Wunsch algorithm at EMBL-EBI services. ( https://www.ebi.ac.uk/Tools/psa/). Although both contain a similar KDKE catalytic tetrad motif and a conserved folding made of a seven-stranded β-sheet surrounded by one to three helices on each side, substantial differences are found in the RNA binding groove as well as the SAM binding pocket (Figure 1C and Figure 2). In CMTR1, Cap0 binds in a deep pocket, with a triphosphate bridge and Cap1 phosphate backbone stabilized by a stack of arginine residues along the RNA binding groove [18]. In contrast, the putative RNA binding groove on SARS- CoV-2 nsp16 appears to be less positively charged and shallow, indicating that the binding of RNA substrate may be unstable (Figure 1C). Even though the SAM binding pocket is conserved between human and viral 2’-O-MTase, they have different structural features. In SARS-CoV-2 nsp16, the SAM binding pocket is more negatively charged than that of CMTR1. Also, the SAM binding pocket on SARS-CoV-2 nsp16 is more open and flexible comparing with that of CMTR1, which is deeper and longer (Figure 1C and 2). In this context, the difference between the structures of the human and 2’-O-MTase CMTR1 and CoV nsp16 could be exploited to develop inhibitors that could specifically block viral methyltransferases [19, 20].

Virtual screening of drugs against nsp16 of SARS-CoV-2 We hypothesize that the small-molecule antagonists of nsp16 of SARS-CoV-2 may be repurposed to limit viral replication and/or unmask viral RNA to intracellular innate immunity. To identify new drugs that have the potential to inhibit nsp16 functions of SARS-CoV-2, we first examined the druggability of all binding sites. DoGSiteScorer (values are between zero and one) was used to calculate geometrical and physicochemical properties such as volume, depth, and hydrophobicity [21]. The SAM pocket has the highest drug score (0.85) and RNA binding pocket has a score of 0.55 in SARS-CoV-2 nsp16 (Supplementary Figure S1). The similar scores were observed in MERS-CoV nsp16 (PDB: 5YNM) that is solved in complex with both SAM and the cap RNA analogue (Supplementary Figure S1).

As the aim of this work was to identify previous clinically investigated and approved drugs for repurposing to treat COVID-19 infections, we made use of an MTiOpenScreen database Drugs- lib that contains 7,173 stereoisomers corresponding to 4574 “approved” drugs [22, 23]. Among them, the nsp16 natural ligand SAM, which is used for therapies against depression, liver disorders, fibromyalgia, and osteoarthritis, would serve as a positive control for virtual screening [24]. Among the five currently available nsp16 structures of SARS-CoV-2 (April 30, 2020), we selected the 6W4H PDB structure which presents the best resolution (1.8 Å) to screen the Drugs- lib using the MTiOpenScreen service [22]. The computations of MTiOpenScreen were carried out with AutoDock Vina, a gradient optimization algorithm, which provided a list of the 1,500 highest-scoring compounds [22, 23, 25]. We repeated the MTiOpenScreen screening protocol three times using the 6W4H structure to ensure the reliability of the results. We found that four stereoisomers of SAM were ranked in the top 1,500 best compounds in all three runs, with energy equal to -8.10 kcal/mol (Figure 3A & B, Supplementary Table S2), indicating our positive docking predictions. Among the 1,500 top hit compounds in each screening, 1,380 compounds were shared across all three MTiOpenScreen runs with highly similar AutoDock Vina scores. Based on the means of scores, we ranked these 1380 compounds (stereoisomers) that correspond to 967 “approved” drugs (Supplementary Table S2). The top ten drugs with the highest scores were MK3207, Rimegepant, Entrectinib, Osi-027, Bolazine, R428, Hesperidin, Losulazine, Rebastinib, and Cep-32496, with the means of energy around -10.97~ -10.17 kcal/mol (Figure 3A and Table 1). Notably, there are 38 Hesperidin stereoisomers and four MK3207 stereoisomers among 1,380 hits (Figure 3A and Supplementary Table S2).

To understand previously reported pharmacological action of hit compounds, we queried the biological target and pathway classes in the Probes and Drugs Portal, in which 713 standardized (693 non-isomeric) drugs were available for these 967 drugs [26]. The top target classes of these drugs are G-protein-coupled receptors (241), catalytic receptors (139), and kinases (129). The top pathways are signal transduction (453), immune system (270), and transcription (247) (Figure 3C). For example, MK3207 and Rimegepant are calcitonin gene-related peptide receptor (CGRP) receptor antagonists, which have been clinically investigated for migraine treatment [27- 31]. Hesperidin possesses biological and pharmacological properties as an effective antioxidant, anti-inflammatory, anti-carcinogenic, and anti-hypertensive agent (Table 1) [32, 33].

Drugs similar to ligand of nsp16

Using the principles of structural similarity searching, analogues of natural ligand (SAM) in nsp16 might be potent inhibitors against 2’-O-MTase function. Since SAM was among our 1,380 highest-scoring compounds, we next computed the similarity between each pair of compounds using the FragFp descriptors in DataWarrior [31]. Among them, we found that seven drugs that are chemically similar to SAM, namely Gs-9667, Trabodenoson, Binodenoson, Sonedenoson, Regadenoson, Metrifudil, and Selodenoson (Figure 3A and Table 2). All seven of these drugs are adenosine receptor agonists that were clinically investigated for treating various diseases, including cardiac arrhythmias, neuropathic pain, inflammatory diseases, and cancer [34, 35]. Additionally, a preprint in ChemRxiv (doi.org/10.26434/chemrxiv.12021330.v1) reported that two of seven drugs, Trabodenoson and Selodenoson, are also identified as potential SARS-CoV- 2 nsp16 inhibitors by computing similarity between 8,085 drugs and SAM with COMPLIG program [36] .

Flexible docking simulation of candidate drugs against nsp16 of SARS-CoV-2

Rigid docking performed using Autodock Vina provided insight into the binding affinity and hydrogen bond formation of the candidate compounds on the nsp16 2’-O-MTase. Next, the top ten drugs and seven drugs structurally similar to SAM were chosen for the ligand flexible docking simulation by using the RosettaLigand program [37, 38]. RosettaLigand employs the Monte Carlo minimization protocol in which the ligand position and orientation are randomly perturbed by a small deviation (0.1 Å and 3°). A scoring function in RosettaLigand includes an electrostatics model, an explicit orientation-dependent hydrogen bonding potential, an implicit solvation model, and van der Walls interactions [37, 38]. Rosetta’s energy score (REU) of these 17 drugs were shown in Table 1 and 2. With RosettaLigand simulation, Hesperidin ranked the highest with the lowest REU among the top 10 hits obtained from the Autodock Vina screening. In the seven SAM-like drugs, similar to AutoDock Vina results, Gs-9667 had the lowest REU score (Table 2).

Binding mode analysis and intermolecular interaction of top drugs and nsp16

We next examined the interaction of these 17 drugs with key residues for nsp16 2’-O-MTase function. We found that Hesperidin, Osi-027, Gs-9667, and Sonedenoson have many hydrogen bonding or hydrophobic interactions with key functional residues involving in 2’-O-MTase function, which are represented in Figure 4 and Supplementary Figure S3. Hesperidin forms hydrogen bonds with N43, K46, D99, L100, C115, D130, Y132, and K170, and hydrophobic interactions with M131. Osi-027 forms hydrogen bonds with N43, K46, D99, L100, N101, Y132, and K170 and hydrophobic interactions with M131, C115, and F149. Gs-9667 forms hydrogen bonds with L100, D114, C115, and Y132, and hydrophobic interactions with L100, M131, and Y132. Sonedenoson forms hydrogen bonds with N43, K46, D75, D99, D130, and K170, and hydrophobic interactions with L100 and M131. Notably, Hesperidin and Sonedenoson form hydrogen bonds with three key residues of KDKE motif: K46, D130 and K170. Based on the ligand-interface interactions, these drugs, notably Hesperidin and Sonedenoson, are worthy of future experimental studies targeting the nsp16 of SARS-CoV-2.

Discussion

In the present study, we analyzed structural features and functional determination of 2’-O- MTase nsp16 of SARS-CoV-2, the newly-identified Betacoronavirus genera, which causes the devastating COVID-19. The nsp16 has a druggable pocket, which is associated with ligand binding and enzymatic activity. By using high-throughput virtual screening against nsp16 of SARS-CoV-2, we have ranked approximately 1,000 therapeutic drugs, including several clinically approved drugs that have the potential to inhibit nsp16 2’-O-MTase and be repurposed for COVID-19 treatment.

Methylation of RNA, which occurs in all kingdoms of life, plays important roles in RNA metabolism, processing, stability, nuclear export, translation efficiency, and others [39-42]. 2′-O- Me is predominantly found in rRNA and tRNA of bacteria and eukaryotes, as well as in the 5' mRNA Cap of higher eukaryotes [43, 44]. In humans, five 2′-O-MTases [FtsJ RNA methyltransferase homolog 1 (FTSJ1), FTSJ2, FTSJ3, CMTR1, and CMTR2] have been reported to catalyze 2’-O-Me of various RNAs, regulate important cellular functions, and are associated with developmental disorders and cancer [45-48]. Mutations of FTSJ1, a tRNA 2′-O-MTase, cause autosomal-recessive intellectual disability [49-51]. FTSJ2 (also known as MRM2) is a mitochondrial rRNA methyltransferase [52]. Human FTSJ3, which likely catalyzes 2’-O-Me of both rRNA and internal sites of mRNA, is a potential regulator of breast cancer progression [53]. Furthermore, FTSJ3 catalyzes 2’-O-Me of HIV RNAs and leads to the inhibition of innate immune sensing and response [45]. Both CMTR1 and CMTR2 catalyze mRNA cap methylation, CMTR1 for cap1 and CMTR2 for cap2. Notably, CMTR1 has previously been identified as ISG95, a protein implicated in the response to interferon treatment and viral infection [54-57]. A very recent study in influenza A virus revealed that loss of CMTR1 in host cells inhibits viral replication and up-regulates anti-viral genes [58]. Thus, 2’-O-MTases have critical roles in viral replication and anti-viral immune response.

Both SARS-CoV-1 and -2 have a single-stranded RNA with ~ 30,000 nucleotides with 5′‐cap structure and 3′‐poly‐A tail (Figure 1A) [1-3]. Many RNA viruses, including CoVs, replicate in the cytoplasm using their own viral 2′-O MTases, such as nsp16, which catalyze the formation of cap structures on viral mRNA that mimic those present on host mRNAs [59, 60]. Previous studies on SARS-CoV-1 and MERS-CoV demonstrated that targeting nsp16 has the potential to interfere with viral replication both at the level of inhibition of the replication process and in promoting intracellular recognition and immune response to viral RNA species [8-10]. Zust et al. determined the role of nsp16 in the viral replication cycle and found that 2’-O-Me acts as a recognition marker that helps the host cell to recognize its own RNA species. Infection studies comparing wild‐type virus and nsp16 mutant CoVs showed that the mutant viruses had decreased replication kinetics but induced higher levels of interferon (IFN) - β [12, 13]. Thus, nsp16-MTase is a promising target for identification of drugs for virus infections, including SARS-CoV-2.

Using virtual screening, we have ranked the predicted binding affinities of approximately 1,000 therapeutic drugs that have potential to inhibit nsp16 2’-O-MTase function. The top hits include MK3207, Rebastinib, Hesperidin, Entrectinib, and Osi-027, which have been experimentally and clinically investigated for treatment of various diseases. Both MK-3207 and Rimegepant are highly-selective CGRP antagonists shown to have potent action against migraine [27-31]. Notably, the orally disintegrating tablet (ODT) formulation of Rimegepant received its first global approval in the USA for the acute treatment of migraine in adults [61]. The exact mechanism of Rimegepant action has yet to be fully characterized, but it has been shown that Rimegepant is a substrate for p-glycoprotein [61]. Entrectinib is an orally available, potent and selective inhibitor of the tyrosine kinases tropomyosin receptor kinases (TRK)A/B/C [62, 63]. Entrectinib was granted breakthrough U.S. FDA approval in 2019 for TRK fusion- positive cancers [62]. Additionally, OSI-027, which allosterically binds to the catalytic site of the kinase domain of mammalian target of rapamycin (mTOR), has demonstrated potent anti-tumor activity in tumor xenografts and is currently undergoing investigation in Phase I clinical trials of patients with advanced cancer [64, 65].

Among the top hits, one of the most promising drugs is Hesperidin, a citrus bioflavonoid, which possesses antioxidant, anti-inflammatory, antiviral, and anticarcinogenic properties [33, 66]. It was used as the pharmaceutical raw material in the pharmaceutical industry and is one of the main components of a Chinese medicine, beniol [67]. Importantly, Hesperidin had demonstrated antiviral properties in in vitro models against influenza A virus (H1N1) by stimulating cell- autonomous immunity through interferon gene expression [68]. Hesperidin also showed promising anti-viral activity against EV-A71 (enterovirus) by enhancing cell survival and reducing viral infection in cells by more than 80%, however the mechanism was not fully characterized [69]. In this study, we found that Hesperidin was the top scoring drug that has the ligand-residue interactions that are critical for nsp16 2’-O-MTase functions. It will be very interesting to determine whether Hesperidin directly binds nsp16 of SARS-CoV-2 with various biochemical approaches and its antiviral activity in cellular and animal models related to COVID-19.

All seven drugs that have similar structures to the nsp16 natural ligand SAM are agonists of the adenosine receptors (ARs). One of them with top AutoDuck and Rosetta scores is Gs-9667, which was clinically investigated for treating Type 2 diabetes. In a phase I study, GS-9667 was generally considered safe and well tolerated [70]. Another interesting hit, Sonedenoson, which facilitates wound healing by regulating the inflammatory response and tissue generation, was evaluated in phase II clinical trials for the treatment of diabetic foot ulcers [70]. Additionally two others, Trabodenoson and Selodenoson, were also reported in a preprint of ChemRxiv (doi.org/10.26434/chemrxiv.12021330.v1) [36]. Given the similar results from both studies, these compounds would be reasonable drugs for further experimental investigation in inhibiting nsp16 2’-O-MTase function.

In conclusion, we analyzed structural features and functional determination of 2’-O-MTase nsp16 of SARS-CoV-2 and employed virtual screening approach for identifying and ranking approximately 1,000 drugs that have the potential to impact nsp16 function. Among them, we found that at least 17 drugs, including Hesperidin and Sonedenoson, merit further testing and repurposing experimentally and/or clinically for COVID-19 treatment.

Material and Methods

Sequence and structure analysis

The primary amino acid sequences of seven human CoV nsp16 proteins and human CMTR1 were retrieved from the NCBI (National Center for Biotechnology Information) Database, and Supplementary Table 1 lists the detailed genome and protein ID for these 2’-O-MTases. The protein sequences were aligned using Clustal Omega (https://www.ebi.ac.uk/Tools/msa/clustalo/), and was presented with the ESPript 3.0 program (http://espript.ibcp.fr/ESPript/ESPript/). Crystal structures of three CoV nsp16s and human CMTR1 were obtained from RCSB Protein Data Bank [5, 6, 15], and analyzed with PyMOL and UCSF Chimera programs. Structural alignment was performed using TM-align algorithm [16].

Virtual screening

Crystal structure (6W4H) of SARS-CoV-2 nsp16 with 1.8 Å resolution was prepared with UCSF Chimera programs for virtual screening against a Drugs-lib that contains 7,173 stereoisomers corresponding to 4,574 “approved” drugs in MTiOpenScreen service [22, 23]. The Drugs-lib is generated from four compound databases of the “drug” subset of the ChEMBL database, the “approved” subset of DrugBank, the DrugCentral database, and the “approved” SuperDrug2 database [22]. For the MTiOpenScreen Vina docking, the (x, y, z) grid center coordinates used for SAM binding pocket of 6W4H are (83.7, 14.8, 27.7), and the size of the search space was set to 20 Å x 20 Å x 20 Å. The MTiOpenScreen screening was repeated three times, and the compounds shared across all three runs was analyzed by DataWarrior, PyMOL, and UCSF Chimera programs. Fragfp descriptors were used to compute the similarity between each pair of compounds [31]. The targets and pathways of identified candidate compounds were analyzed by querying Probes and Drugs Portal.

Flexible docking simulation in RosettaLigand program

Ligand flexible docking simulation were performed by using the RosettaLigand program that employs the Monte Carlo minimization protocol [37, 38]. In the first, low-resolution stage, the ligand is placed near the SAM binding pocket, where it is perturbed 50 times and rotated 1000 times in a random direction. The best-scoring models are filtered by root-mean-square deviation to eliminate near duplicates and one of the remaining models is selected at random. To ensure that the ligand did not “walk away” from the protein, the ligand is moved towards the protein. The second, high-resolution stage employs the Monte Carlo minimization protocol in which the ligand position and orientation are randomly perturbed by a small deviation (0.1 Å and 3°); receptor side chains are repacked using a rotamer library; the ligand position, orientation, and torsions and protein side-chain torsions are simultaneously optimized using quasi-Newton minimization and the end result is accepted or rejected based on the Metropolis criterion. Scoring uses the full-atom Rosetta energy function with softened van der Waals repulsion [37, 38]. The full repack makes 1000 random rotamer substitutions at random positions and accepts or rejects each on the Metropolis criterion. Rotamer trials choose the single best rotamer at a random position in the context of the current state of the rest of the system, with the positions visited once each in random order. Six cycles of rotamer trials and a full repack after every three cycles are performed. The third and final stage is a more stringent gradient-based minimization of the ligand position, orientation, and torsions and receptor torsions for both side chains and backbone. Scoring uses the same Rosetta energy function, but with a hard-repulsive van der Waals potential, which creates a more rugged energy landscape that is better at discriminating native from non-native binding modes [37, 38]. The entire structure is then scored using the partial covalent interactions energy function, which is developed to score H-bonds more accurately.

Conflict of interest The authors have no competing interests to declare.

Acknowledgments This work was partially supported by grants from the Department of Defense (DoD) Breast Cancer Program BC161536, Elsa U. Pardee Foundation, DMC Foundation and Molecular Therapeutics Program of Karmanos Cancer Institute to Dr. Zeng-Quan Yang; and by funding from Susan G. Komen GTDR14299438 and Wayne State University Graduate School Dean Mathur Fellowship to Morenci Manning.

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Figure Legends:

Figure 1: Comparative analysis of primary amino acid sequences and crystal structures of CoV 2’-O-MTases. (A) Schematic presentation of the SARS-CoV-2 genome organization. Expression of two open reading frames (ORF1a and ORF1b) yields 16 nsps, including 2’-O-MTase nsp16. S, E, M, and N indicate the four structural proteins spike, envelope, membrane, and nucleocapsid. (B) Sequence alignment of nsp16 proteins derived from genome sequences of the following: SARS-CoV-2, SARS-CoV-1, MERS-CoV, HCoV-OC43, HCoV-HKU1, HCoV- NL63, and HCoV-229E. The secondary structure of SARS-CoV-2 nsp16 is shown above. Residues with 100% conservation are indicated in solid red boxes and those with identity of 70% or higher are depicted in light red color. The red stars indicate the conserved KDKE motif in 2’- O-MTases. (C) Surface representation of the SAM binding pocket and the putative RNA binding groove in SARS-CoV-2 nsp16 with coloring according to the electrostatic potential. The surface electrostatic potential diagram (±5 kT/e) was generated by PyMol; the blue areas represent positively charged areas, while the red areas represent negatively charged areas. (D) The KDKE catalytic tetrad motif is located at the bottom of the RNA binding groove.

Figure 2: Comparison 2’-O-MTase domain of human CMTR1 with nsp16 of SARS-CoV-2. Top: Surface representation with electrostatic potentials showing the RNA binding groove and the SAM binding pocket of human CMTR1 (PDB: 4N48). Bottom: Superposition of the KDKE catalytic tetrad motifs of nsp16 of SARS-CoV-2 (PDB: 6W4H) and 2’-O-MTase domain of human CMTR1 (PDB: 4N48).

Figure 3. (A) Similarity chart of the 1380 best scored compounds for the SARS-CoV-2 nsp16 using the FragFp descriptors in DataWarrior. Compounds with high chemical similarity are connected by lines. Stereoisomers of same drug such as Hesperidin (38 Stereoisomers) are clustered together. Compounds are colored according to their predicted AutoDock Vina score. (B) Neighbor tree shows seven drugs that have FragFp similarity scores greater than 0.8. Drugs are colored according to their FragFp similarity score to SAM. (C) Pie charts show target and pathway classes of hit compounds that were queried in the Probes and Drugs Portal.

Figure 4. Interaction of Hesperidin and Sonedenoson with SAM binding pocket of SARS-CoV-2 nsp16. Left: Surface representation with charge showing predicted binding of SARS-CoV-2 nsp16 with Hesperidin and Sonedenoson in the SAM binding pocket. Hesperidin and Sonedenoson are depicted by sticks. Middle: 3D representation of 2’-O-MTase active site residues interacting with Hesperidin and Sonedenoson. Right: 2D representation of 2’-O-MTase active site residues interacting with Hesperidin and Sonedenoson.

Supplementary Figure Legends: Figure S1. The three-dimensional (3D) structures of nsp16s of SARS-CoV-2 (PDB: 6W4H) and MERS-CoV (PDB: 5YNM) were solved in complex with nsp10. RNA and SAM binding pockets were detected by DoGSiteScorer tool of the ProteinsPlus server.

Figure S2. The RNA and SAM binding sites in nsp16 of MERS-CoV (PDB: 5YNM).

Figure S3. Interaction of Hesperidin and Sonedenoson with SAM binding pocket of SARS-CoV- 2 nsp16. Left: Surface representation with charge showing predicted binding of SARS-CoV-2 nsp16 with Osi-027 and Gs-9667 in the SAM binding pocket. Osi-027 and Gs-9667 are depicted by sticks. 3D representation of 2’-O-MTase active site residues interacting with Osi-027 and Gs- 9667. Right: 2D representation of 2’-O-MTase active site residues interacting with Osi-027 and Gs-9667.

NSP16 full manuscript (5-6-2020)_Submitted Version.pdf (8.30 MiB) view on ChemRxiv download file

Table S1. 2'-O-methyltransferases employed in this study along with the relative details Name NCBI ID (TAX or Gene) NCBI Genome Protein GI (Domain location) RCSB PDB SARS-CoV-2 nsp16 2697049 NC_045512 YP_009725311.1 6W4H,6WKQ, 6WJT, 6W75, 6W61 SARS-CoV-1 nsp16 694009 NC_004718.3 NP_828873.2 3R24, 2XYR, 2XYQ, 2XYV, 2XYR 5YNM, 5YNF, 5YNN,5YN6, 5YNQ, MERS-CoV nsp16 1335626 NC_019843.3 YP_009047227.1 5YN5, 5YNO, 5YN8, 5YNB, 5YNJ, 5YNI, 5YNP HCoV-OC43 31631 NC_006213 YP_009555238.1 HCoV-HKU1 290028 NC_006577.2 YP_460023.1 HCoV-NL63 277944 NC_005831.2 YP_003766.2 HCV-229E 11137 NC_002645 NP_073549.1 Human CMTR1 23070 NM_015050.3 NP_055865.1 (Location:232 → 448) 4N48, 4N49, 4N4A Table S2. List of the 1,380 highest-scoring compounds in three MTiOpenScreen runs

MTiOpenScreen_ MTiOpenScreen_ MTiOpenScreen_ Score Ranking Drug_Name ZINC_ID Means of Energies Run#1_Energy Run#2_Energy Run#3_Energy 1 Mk3207 ZINC000043203371 -11 -11 -10.9 -10.97 2 Mk3207 ZINC000103760978 -11 -10.9 -10.9 -10.93 3 Rimegepant ZINC000068267814 -10.8 -10.7 -10.8 -10.77 4 Entrectinib ZINC000043204146 -10.6 -10.5 -10.6 -10.57 5 Osi-027 ZINC000252286769 -10.5 -10.5 -10.5 -10.50 6 Bolazine ZINC000008214506 -10.4 -10.5 -10.5 -10.47 7 R428 ZINC000051951669 -10.4 -10.4 -10.4 -10.40 8 R428 ZINC000051951668 -10.4 -10.4 -10.4 -10.40 9 Mk3207 ZINC000103760981 -10.4 -10.4 -10.4 -10.40 10 Hesperidin ZINC000100204053 -10.3 -10.3 -10.3 -10.30 11 Losulazine ZINC000004216779 -10.2 -10.3 -10.3 -10.27 12 Rebastinib ZINC000063933734 -10.2 -10.2 -10.2 -10.20 13 Hesperidin ZINC000038144571 -10.2 -10.2 -10.2 -10.20 14 Cep-32496 ZINC000043207440 -10.2 -10.2 -10.2 -10.20 15 Hesperidin ZINC000038144570 -10.1 -10.2 -10.2 -10.17 16 Gedatolisib ZINC000049757175 -10.1 -10 -10.2 -10.10 17 Hesperidin ZINC000252008997 -10.1 -10.1 -10.1 -10.10 18 Dihydroergocristine ZINC000003947494 -10.1 -10.1 -10.1 -10.10 19 Hesperidin ZINC000038144568 -10.1 -10.1 -10.1 -10.10 20 Hesperidin ZINC000238924079 -10.1 -10.1 -10.1 -10.10 21 Hesperidin ZINC000038144569 -10.1 -10.1 -10.1 -10.10 22 Orvepitant ZINC000056898864 -10.1 -10.1 -10.1 -10.10 23 Tg100-801 ZINC000029136020 -10.1 -10 -10.1 -10.07 24 Hesperidin ZINC000252009000 -10 -10 -10 -10.00 25 Mk3207 ZINC000103760984 -10 -10 -10 -10.00 26 Bencianol ZINC000004214953 -10 -10 -10 -10.00 27 Hesperidin ZINC000100204061 -10 -10 -10 -10.00 28 Ditercalinium ZINC000004215707 -9.9 -10.1 -10 -10.00 29 Hesperidin ZINC000103938990 -10 -10 -10 -10.00 30 Gepotidacin ZINC000223227887 -10 -10 -10 -10.00 31 Zoliflodacin ZINC000145806066 -10 -10 -10 -10.00 32 Bisoctrizole ZINC000011677911 -10 -10 -9.9 -9.97 33 Entospletinib ZINC000098208742 -10 -9.9 -9.9 -9.93 34 Nrx195183 ZINC000001909562 -9.9 -10 -9.9 -9.93 35 Setipafant ZINC000001481922 -9.9 -9.9 -9.9 -9.90 36 Hesperidin ZINC000103939005 -9.9 -9.9 -9.9 -9.90 37 Disogluside ZINC000008214547 -9.9 -9.9 -9.9 -9.90 38 Hesperidin ZINC000253499897 -9.9 -9.9 -9.9 -9.90 39 Hesperidin ZINC000008680006 -9.9 -9.9 -9.9 -9.90 40 Lixivaptan ZINC000000600399 -9.9 -9.9 -9.9 -9.90 41 Hesperidin ZINC000238924078 -9.9 -9.9 -9.9 -9.90 42 Proscillaridin ZINC000038139432 -9.9 -9.9 -9.9 -9.90 43 Merestinib ZINC000095926668 -9.8 -9.9 -9.9 -9.87 44 Hesperidin ZINC000252008995 -9.9 -9.9 -9.8 -9.87 45 Hesperidin ZINC000103938984 -9.9 -9.9 -9.8 -9.87 46 Venetoclax ZINC000150338755 -9.8 -9.9 -9.8 -9.83 47 Spirofylline ZINC000084758966 -9.7 -9.8 -9.9 -9.80 48 Hesperidin ZINC000100204058 -9.8 -9.8 -9.8 -9.80 49 alpha_Ergocryptine ZINC000222341315 -9.8 -9.8 -9.8 -9.80 50 Hesperidin ZINC000008680007 -9.8 -9.8 -9.8 -9.80 51 Tivantinib ZINC000100016063 -9.8 -9.8 -9.8 -9.80 52 Hesperidin ZINC000095568264 -9.8 -9.8 -9.8 -9.80 53 Osi-027 ZINC000068203220 -9.8 -9.8 -9.8 -9.80 54 Tegobuvir ZINC000100057121 -9.8 -9.8 -9.8 -9.80 55 Hesperidin ZINC000100204049 -9.8 -9.8 -9.8 -9.80 56 Prulifloxacin ZINC000000596006 -9.8 -9.8 -9.8 -9.80 57 Ibutamoren ZINC000001543181 -9.8 -9.8 -9.8 -9.80 58 Erismodegib ZINC000068202099 -9.8 -9.7 -9.8 -9.77 59 Hesperidin ZINC000253499898 -9.8 -9.7 -9.8 -9.77 60 Ag-13958 ZINC000034037183 -9.7 -9.9 -9.7 -9.77 61 Fiduxosin ZINC000029747110 -9.6 -9.8 -9.8 -9.73 62 Mosapramine ZINC000000597691 -9.9 -9.9 -9.4 -9.73 63 Cortisuzol ZINC000004215464 -9.7 -9.7 -9.8 -9.73 64 Gepotidacin ZINC000138562667 -9.7 -9.7 -9.7 -9.70 65 Ripisartan ZINC000000538309 -9.7 -9.7 -9.7 -9.70 66 Zosuquidar ZINC000100029945 -9.7 -9.7 -9.7 -9.70 67 Seganserin ZINC000000538333 -9.7 -9.7 -9.7 -9.70 68 Metergotamine ZINC000072266819 -9.7 -9.7 -9.7 -9.70 69 Dihydroergotamine ZINC000003978005 -9.7 -9.7 -9.7 -9.70 70 Talmetacin ZINC000001846459 -9.7 -9.7 -9.7 -9.70 71 Linsitinib ZINC000100071817 -9.7 -9.7 -9.7 -9.70 72 Setileuton ZINC000036487556 -9.7 -9.7 -9.7 -9.70 73 Dihydroergocristine ZINC000003947497 -9.7 -9.7 -9.7 -9.70 74 Proscillaridin ZINC000306121901 -9.7 -9.7 -9.7 -9.70 75 Omipalisib ZINC000043208634 -9.7 -9.7 -9.7 -9.70 76 Hesperidin ZINC000253499899 -9.8 -9.8 -9.4 -9.67 77 Capmatinib ZINC000043195321 -9.7 -9.6 -9.7 -9.67 78 Ac-480 ZINC000072190221 -9.6 -9.7 -9.7 -9.67 79 Etoposide-phosphate ZINC000575418368 -9.7 -9.7 -9.6 -9.67 80 Hesperidin ZINC000049889104 -9.8 -9.8 -9.3 -9.63 81 Dabrafenib ZINC000068153186 -9.7 -9.6 -9.6 -9.63 82 Ly-2584702 ZINC000043204100 -9.6 -9.7 -9.6 -9.63 83 Etoposide ZINC000135672818 -9.7 -9.6 -9.6 -9.63 84 Golvatinib ZINC000043195317 -9.7 -9.7 -9.5 -9.63 85 Solcitinib ZINC000118401631 -9.9 -8.9 -10 -9.60 86 Hesperidin ZINC000252008992 -9.4 -9.6 -9.8 -9.60 87 Hesperidin ZINC000253499896 -9.6 -9.6 -9.6 -9.60 88 Doxazosin ZINC000094566093 -9.6 -9.6 -9.6 -9.60 89 Ergotamine ZINC000052955754 -9.6 -9.6 -9.6 -9.60 90 Teniposide ZINC000202773837 -9.6 -9.6 -9.6 -9.60 91 Hesperidin ZINC000103938998 -9.6 -9.6 -9.6 -9.60 92 Prulifloxacin ZINC000001269201 -9.6 -9.6 -9.6 -9.60 93 Amg-900 ZINC000043208325 -9.6 -9.6 -9.6 -9.60 94 Lurasidone ZINC000003927822 -9.6 -9.6 -9.6 -9.60 95 Dovitinib ZINC000003816310 -9.6 -9.6 -9.6 -9.60 96 Hesperidin ZINC000238924080 -9.6 -9.6 -9.6 -9.60 97 Rimacalib ZINC000004423231 -9.6 -9.6 -9.6 -9.60 98 Mosapramine ZINC000003873789 -9.6 -9.6 -9.6 -9.60 99 Paliperidone ZINC000004214700 -9.6 -9.5 -9.6 -9.57 100 Itriglumide ZINC000001544617 -9.6 -9.6 -9.5 -9.57 101 Novobiocin ZINC000076945632 -9.5 -9.6 -9.6 -9.57 102 Hesperidin ZINC000067902505 -9.5 -9.6 -9.6 -9.57 103 Hesperidin ZINC000097972618 -9.7 -9.8 -9.2 -9.57 104 Conivaptan ZINC000012503187 -9.5 -9.6 -9.5 -9.53 105 Lestaurtinib ZINC000003781738 -9.5 -9.5 -9.5 -9.50 106 Dihydroergocryptine ZINC000003929793 -9.5 -9.5 -9.5 -9.50 107 Butaclamol ZINC000040933021 -9.5 -9.5 -9.5 -9.50 108 Vs-5584 ZINC000049090010 -9.5 -9.5 -9.5 -9.50 109 Proscillaridin ZINC000257355132 -9.5 -9.5 -9.5 -9.50 110 Lodiperone ZINC000053149862 -9.5 -9.5 -9.5 -9.50 111 Talmetacin ZINC000000608088 -9.5 -9.5 -9.5 -9.50 112 Tasosartan ZINC000013444037 -9.5 -9.5 -9.5 -9.50 113 Verubecestat ZINC000144542146 -9.5 -9.5 -9.5 -9.50 114 alpha_Ergocryptine ZINC000059796556 -9.5 -9.5 -9.5 -9.50 115 Hesperidin ZINC000104889096 -9.5 -9.5 -9.5 -9.50 116 Ac-480 ZINC000006717782 -9.5 -9.5 -9.5 -9.50 117 Pf-00477736 ZINC000137899389 -9.4 -9.4 -9.6 -9.47 118 Efatutazone ZINC000033975065 -9.4 -9.5 -9.5 -9.47 119 Revefenacin ZINC000113648937 -9.6 -9.3 -9.5 -9.47 120 Dihydroergocristine ZINC000003947495 -9.4 -9.5 -9.5 -9.47 121 Tarazepide ZINC000002015955 -9.5 -9.4 -9.5 -9.47 122 Enmd-2076 ZINC000034885047 -9.4 -9.5 -9.5 -9.47 123 Chir-265 ZINC000018710085 -9.6 -9.4 -9.4 -9.47 124 Pf-03715455 ZINC000082138051 -9.6 -9.6 -9.2 -9.47 125 Hesperidin ZINC000008382286 -9.2 -10 -9.2 -9.47 126 Azd3514 ZINC000101673084 -9.5 -9.4 -9.4 -9.43 127 Teniposide ZINC000077313309 -9.4 -9.4 -9.5 -9.43 128 Milciclib ZINC000053119602 -9.4 -9.5 -9.4 -9.43 129 Raltegravir ZINC000013831130 -9.5 -9.7 -9.1 -9.43 130 Hesperidin ZINC000085340597 -9.5 -9.1 -9.6 -9.40 131 Azd-8055 ZINC000095567488 -9.4 -9.4 -9.4 -9.40 132 Olaparib ZINC000040430143 -9.4 -9.4 -9.4 -9.40 133 Pictilisib ZINC000016052714 -9.4 -9.4 -9.4 -9.40 134 Pazopanib ZINC000011617039 -9.4 -9.4 -9.4 -9.40 135 Floxacrine ZINC000001846338 -9.4 -9.4 -9.4 -9.40 136 Etoposide ZINC000100023533 -9.4 -9.4 -9.4 -9.40 137 Ziprasidone ZINC000000538550 -9.4 -9.4 -9.4 -9.40 138 Lumacaftor ZINC000064033452 -9.4 -9.4 -9.4 -9.40 139 Floxacrine ZINC000000607874 -9.4 -9.4 -9.4 -9.40 140 Axamozide ZINC000004212030 -9.4 -9.4 -9.4 -9.40 141 Flumatinib ZINC000068244727 -9.4 -9.4 -9.4 -9.40 142 Lurtotecan ZINC000022010625 -9.4 -9.4 -9.4 -9.40 143 Hesperidin ZINC000247658398 -9.4 -9.4 -9.4 -9.40 144 Proscillaridin ZINC000118917543 -9.4 -9.4 -9.4 -9.40 145 Linifanib ZINC000006718813 -9.4 -9.4 -9.4 -9.40 146 Mln-8054 ZINC000018825334 -9.4 -9.4 -9.4 -9.40 147 Mk-0893 ZINC000095574316 -9.3 -9.3 -9.5 -9.37 148 Talniflumate ZINC000001844627 -9.3 -9.3 -9.5 -9.37 149 Gilteritinib ZINC000113476229 -9.3 -9.4 -9.4 -9.37 150 Hesperidin ZINC000248139797 -9.4 -9.3 -9.4 -9.37 151 Brazergoline ZINC000004215062 -9.3 -9.4 -9.4 -9.37 152 Barmastine ZINC000004214938 -9.4 -9.3 -9.4 -9.37 153 Azd-8055 ZINC000052509466 -9.4 -9.4 -9.3 -9.37 154 Proscillaridin ZINC000008143879 -9.3 -9.4 -9.3 -9.33 155 Fluspirilene ZINC000000537755 -9.4 -9.3 -9.3 -9.33 156 Cromolyn ZINC000001530788 -9.4 -9.3 -9.3 -9.33 157 Ubrogepant ZINC000095598454 -9.3 -9.3 -9.3 -9.30 158 Aminoquinuride ZINC000022910880 -9.3 -9.3 -9.3 -9.30 159 At-9283 ZINC000038995988 -9.3 -9.3 -9.3 -9.30 160 Bifeprunox ZINC000052971454 -9.3 -9.3 -9.3 -9.30 161 Nilotinib ZINC000006716957 -9.3 -9.3 -9.3 -9.30 162 Exatecan ZINC000003800855 -9.3 -9.3 -9.3 -9.30 163 Proscillaridin ZINC000118917544 -9.3 -9.3 -9.3 -9.30 164 Pf-00477736 ZINC000019862643 -9.3 -9.3 -9.3 -9.30 165 Rupatadine ZINC000000598829 -9.3 -9.3 -9.3 -9.30 166 Proscillaridin ZINC000257488919 -9.3 -9.3 -9.3 -9.30 167 ZINC000105284878 ZINC000105284878 -9.3 -9.3 -9.3 -9.30 168 Azd-2014 ZINC000049019448 -9.3 -9.3 -9.3 -9.30 169 Etoposide ZINC000100023538 -9.3 -9.3 -9.3 -9.30 170 Doxazosin ZINC000094566092 -9.3 -9.3 -9.3 -9.30 171 Abamectin-component-b1a ZINC000252673974 -9.3 -9.3 -9.3 -9.30 172 Tadalafil ZINC000000538404 -9.3 -9.3 -9.3 -9.30 173 Fluazuron ZINC000002570819 -9.3 -9.3 -9.3 -9.30 174 Piperaquine ZINC000026251015 -9.3 -9.3 -9.3 -9.30 175 Tak-593 ZINC000095579919 -9.3 -9.4 -9.2 -9.30 176 Glisindamide ZINC000000537799 -9.2 -9.1 -9.5 -9.27 177 Lifitegrast ZINC000084668739 -9.2 -9.2 -9.4 -9.27 178 Pf-03758309 ZINC000043203531 -9.2 -9.2 -9.4 -9.27 179 Telithromycin ZINC000009574770 -9.2 -9.3 -9.3 -9.27 180 Mk-2461 ZINC000034842286 -9.2 -9.3 -9.3 -9.27 181 Uk432097 ZINC000150664074 -9.4 -9 -9.4 -9.27 182 Mk-2461 ZINC000034842284 -9.3 -9.2 -9.2 -9.23 183 Cep-11981 ZINC000036411318 -9.2 -9.3 -9.2 -9.23 184 Talmapimod ZINC000034001955 -9.2 -9.3 -9.2 -9.23 185 Xaliproden ZINC000000577115 -9.3 -9.2 -9.2 -9.23 186 Teniposide ZINC000004099009 -9.2 -9.2 -9.2 -9.20 187 Metesind ZINC000000537989 -9.2 -9.2 -9.2 -9.20 188 Bms-833923 ZINC000096170449 -9.2 -9.2 -9.2 -9.20 189 Irbesartan ZINC000003872931 -9.2 -9.2 -9.2 -9.20 190 Elomotecan ZINC000003921664 -9.2 -9.2 -9.2 -9.20 191 Nms-1286937 ZINC000049113058 -9.2 -9.2 -9.2 -9.20 192 Teniposide ZINC000003831506 -9.2 -9.2 -9.2 -9.20 193 Ritanserin ZINC000000538314 -9.2 -9.2 -9.2 -9.20 194 Hesperidin ZINC000008382287 -9.2 -9.2 -9.2 -9.20 195 Netupitant ZINC000011681563 -9.2 -9.2 -9.2 -9.20 196 Dihydroergocristine ZINC000003947496 -9.2 -9.2 -9.2 -9.20 197 Troglitazone ZINC000000968276 -9.2 -9.2 -9.2 -9.20 198 Taselisib ZINC000068267049 -9.2 -9.2 -9.2 -9.20 199 ZINC000059796557 ZINC000059796557 -9.2 -9.2 -9.2 -9.20 200 Casopitant ZINC000042856596 -9.2 -9.2 -9.2 -9.20 201 Etriciguat ZINC000000603759 -9.2 -9.2 -9.2 -9.20 202 Hesperidin ZINC000008143568 -9.2 -9.2 -9.2 -9.20 203 Israpafant ZINC000003776441 -9.2 -9.2 -9.2 -9.20 204 Furomazine ZINC000000607904 -9.2 -9.2 -9.2 -9.20 205 Radiprodil ZINC000028363953 -9.2 -9.2 -9.2 -9.20 206 Dihydroergocristine ZINC000003995616 -9.2 -9.2 -9.2 -9.20 207 Irinotecan ZINC000001612996 -9.2 -9.1 -9.2 -9.17 208 Cetefloxacin ZINC000003779887 -9.1 -9.2 -9.2 -9.17 209 Mergocriptine ZINC000072266905 -9.2 -9.1 -9.2 -9.17 210 Ataciguat ZINC000003612878 -9.1 -9.2 -9.2 -9.17 211 Basmisanil ZINC000145814743 -9.1 -9.2 -9.2 -9.17 212 Abemaciclib ZINC000072318121 -9.1 -9.2 -9.2 -9.17 213 Mk-6592 ZINC000043153387 -9.1 -9.2 -9.2 -9.17 214 Etoposide ZINC000103553205 -9.2 -9.1 -9.2 -9.17 215 Tameridone ZINC000000538412 -9.2 -9.2 -9.1 -9.17 216 Teniposide ZINC000003831507 -9.2 -9.2 -9.1 -9.17 217 Aleplasinin ZINC000013580622 -9.2 -9.2 -9.1 -9.17 218 Quilostigmine ZINC000056897587 -9.1 -9.1 -9.2 -9.13 219 Giripladib ZINC000085537113 -9.2 -9.1 -9.1 -9.13 220 Xl-019 ZINC000095930152 -9.2 -9.1 -9.1 -9.13 221 Gsk163090 ZINC000034451922 -9.1 -9.2 -9.1 -9.13 222 Flezelastine ZINC000001534968 -9.1 -9.2 -9.1 -9.13 223 Ag-13958 ZINC000095909141 -9.1 -9.2 -9.1 -9.13 224 Burapitant ZINC000003990019 -9.2 -9.1 -9.1 -9.13 225 Xl-019 ZINC000095560529 -9.2 -9.1 -9.1 -9.13 226 Hesperidin ZINC000248139800 -9 -9.4 -9 -9.13 227 Posaconazole ZINC000003938482 -9 -9 -9.3 -9.10 228 Diosmin ZINC000004098512 -9.2 -8.9 -9.2 -9.10 229 Afacifenacin ZINC000001554383 -8.9 -9.2 -9.2 -9.10 230 Proscillaridin ZINC000118915484 -9.1 -9.1 -9.1 -9.10 231 Lomitapide ZINC000027990463 -9.1 -9.1 -9.1 -9.10 232 beta_Ergocryptine ZINC000064633860 -9.1 -9.1 -9.1 -9.10 233 Tosufloxacin ZINC000021983589 -9.1 -9.1 -9.1 -9.10 234 Liafensine ZINC000095598450 -9.1 -9.1 -9.1 -9.10 235 Mioflazine ZINC000022463073 -9.2 -9 -9.1 -9.10 236 Tadalafil ZINC000008204642 -9.1 -9.1 -9.1 -9.10 237 Ocaperidone ZINC000000538119 -9.1 -9.1 -9.1 -9.10 238 Ag-24322 ZINC000200158122 -9.1 -9.1 -9.1 -9.10 239 Tosufloxacin ZINC000021983587 -9.1 -9.1 -9.1 -9.10 240 Brequinar ZINC000001587011 -9.1 -9.1 -9.1 -9.10 241 beta_Ergocryptine ZINC000059213491 -9.1 -9.1 -9.1 -9.10 242 Cadazolid ZINC000043195938 -9.1 -9.1 -9.1 -9.10 243 Alisertib ZINC000040939534 -9.1 -9.1 -9.1 -9.10 244 Dolutegravir ZINC000058581064 -9.1 -9.1 -9.1 -9.10 245 Taprostene ZINC000004217507 -9.1 -9.1 -9.1 -9.10 246 Zaldaride ZINC000002016009 -9.1 -9.1 -9.1 -9.10 247 Teniposide ZINC000202773821 -9.1 -9.1 -9.1 -9.10 248 Belaperidone ZINC000003822014 -9.1 -9.1 -9.1 -9.10 249 Etoposide-phosphate ZINC000618072474 -9.1 -9.1 -9.1 -9.10 250 Deferasirox ZINC000001481815 -9.1 -9.1 -9.1 -9.10 251 Amg-208 ZINC000034285235 -9.1 -9.1 -9.1 -9.10 252 Azd-8055 ZINC000143201183 -9.1 -9.1 -9.1 -9.10 253 Hesperidin ZINC000008214774 -9.1 -9.1 -9.1 -9.10 254 Calcipotriene ZINC000003921872 -9.1 -9.1 -9.1 -9.10 255 Romergoline ZINC000003782563 -9.1 -9.1 -9.1 -9.10 256 Proscillaridin ZINC000118915483 -9.1 -9.1 -9.1 -9.10 257 Bromocriptine ZINC000053683151 -9.1 -9.1 -9.1 -9.10 258 Darglitazone ZINC000001492464 -9.1 -9.1 -9.1 -9.10 259 Guadecitabine ZINC000575627124 -9.1 -9.1 -9.1 -9.10 260 Sanguinarium ZINC000000000706 -9.1 -9.1 -9.1 -9.10 261 Aprepitant ZINC000043770784 -9.1 -9.1 -9.1 -9.10 262 Yohimbic-acid ZINC000005776998 -9.1 -9.1 -9.1 -9.10 263 Dihydroergocristine ZINC000095862766 -9.1 -9.1 -9.1 -9.10 264 baicalin ZINC000003943903 -9.1 -9.1 -9.1 -9.10 265 Guadecitabine ZINC000257351737 -9.3 -9 -9 -9.10 266 Icopezil-maleate ZINC000000537848 -9.1 -9 -9.1 -9.07 267 Devazepide ZINC000001847292 -9.1 -9 -9.1 -9.07 268 Posizolid ZINC000003982517 -9.1 -9 -9.1 -9.07 269 Efipladib ZINC000085536943 -9.1 -9.1 -9 -9.07 270 Radotinib ZINC000059749972 -9.1 -9.1 -9 -9.07 271 Etoposide ZINC000079228615 -9 -9.1 -9.1 -9.07 272 Silmitasertib ZINC000058638454 -9 -9.1 -9.1 -9.07 273 Trelanserin ZINC000000602552 -9 -9.2 -9 -9.07 274 Altiratinib ZINC000113198271 -9 -9.2 -9 -9.07 275 Telatinib ZINC000000590964 -9.2 -9.1 -8.9 -9.07 276 Uk432097 ZINC000095539256 -8.8 -9.1 -9.2 -9.03 277 Etoposide ZINC000004245621 -9 -9 -9.1 -9.03 278 Fludoxopone ZINC000000537737 -9 -9 -9.1 -9.03 279 Nicergoline ZINC000003873817 -9 -9.1 -9 -9.03 280 Taladegib ZINC000068247898 -9.1 -9 -9 -9.03 281 Fananserin ZINC000000597400 -9 -9.1 -9 -9.03 282 Zoloperone ZINC000036093059 -9 -9.1 -9 -9.03 283 Anatibant ZINC000053261548 -8.9 -9.2 -9 -9.03 284 Paliroden ZINC000035826853 -9 -9.1 -9 -9.03 285 Capeserod ZINC000000603773 -9.1 -9 -9 -9.03 286 Telcagepant ZINC000028827350 -9.1 -9 -9 -9.03 287 Vemurafenib ZINC000052509366 -9.1 -9 -9 -9.03 288 Jnj-38877605 ZINC000043170515 -9.1 -9 -9 -9.03 289 Regorafenib ZINC000006745272 -9 -8.8 -9.2 -9.00 290 Dofequidar ZINC000013652236 -8.9 -9 -9.1 -9.00 291 Enpiroline ZINC000001568035 -9 -9 -9 -9.00 292 Halopemide ZINC000000537818 -9 -9 -9 -9.00 293 Cenisertib ZINC000063298059 -9 -9 -9 -9.00 294 Omarigliptin ZINC000084758480 -9 -9 -9 -9.00 295 Icotinib ZINC000043207566 -9 -9 -9 -9.00 296 Pomisartan ZINC000150340377 -9 -9 -9 -9.00 297 Granisetron ZINC000100018852 -9 -9 -9 -9.00 298 Enpiroline ZINC000004628938 -9 -9 -9 -9.00 299 Fenoverine ZINC000019899628 -9 -9 -9 -9.00 300 Minalrestat ZINC000001492564 -9 -9 -9 -9.00 301 Metoquizine ZINC000000607966 -9 -9 -9 -9.00 302 Aee-788 ZINC000022453679 -9 -9 -9 -9.00 303 Clopimozide ZINC000004215428 -9 -9 -9 -9.00 304 Dasabuvir ZINC000095616937 -9 -9 -9 -9.00 305 Fosaprepitant ZINC000003939013 -9 -9 -9 -9.00 306 Sabiporide ZINC000033999019 -9 -9 -9 -9.00 307 Gsk-461364 ZINC000043154472 -9 -9 -9 -9.00 308 Mavatrep ZINC000043175494 -9 -9 -9 -9.00 309 Altapizone ZINC000006096074 -9 -9 -9 -9.00 310 Befetupitant ZINC000028570456 -9 -9 -9 -9.00 311 Ar-12 ZINC000003960083 -9 -9 -9 -9.00 312 Revaprazan ZINC000003633836 -9 -9 -9 -9.00 313 Cp-724714 ZINC000003817105 -9 -9 -9 -9.00 314 Iloperidone ZINC000001548097 -9 -9 -9 -9.00 315 Adapalene ZINC000003784182 -9 -9 -9 -9.00 316 Guadecitabine ZINC000257351738 -9 -9 -9 -9.00 317 Scopinast ZINC000003944646 -9 -9 -9 -9.00 318 Troglitazone ZINC000000968278 -9 -9 -9 -9.00 319 Bi-2536 ZINC000013986815 -9 -9 -9 -9.00 320 Calcipotriene ZINC000004654793 -9 -9 -9 -9.00 321 Elinogrel ZINC000043153259 -9 -9 -9 -9.00 322 Penfluridol ZINC000004217252 -9 -9.1 -8.9 -9.00 323 Risperidone ZINC000000538312 -9 -9.1 -8.9 -9.00 324 Palovarotene ZINC000038467831 -9.1 -9 -8.9 -9.00 325 Tivozanib ZINC000001489430 -9.2 -8.9 -8.9 -9.00 326 Ropitoin ZINC000011682492 -8.7 -9.2 -9.1 -9.00 327 Teniposide ZINC000004099008 -9.7 -8.7 -8.6 -9.00 328 Gliquidone ZINC000001482077 -8.8 -8.9 -9.2 -8.97 329 Upidosin ZINC000003796141 -9 -8.8 -9.1 -8.97 330 Izonsteride ZINC000001544066 -8.9 -8.9 -9.1 -8.97 331 Sorafenib ZINC000001493878 -8.9 -9 -9 -8.97 332 alpha_Ergocryptine ZINC000014952151 -9 -8.9 -9 -8.97 333 Bafetinib ZINC000022940637 -9 -8.9 -9 -8.97 334 Lifarizine ZINC000019368434 -8.9 -9 -9 -8.97 335 Balaglitazone ZINC000001481805 -8.9 -9 -9 -8.97 336 Flibanserin ZINC000052716421 -8.9 -9 -9 -8.97 337 Pf-04217903 ZINC000043195316 -9 -8.9 -9 -8.97 338 Ibodutant ZINC000028711707 -9 -9 -8.9 -8.97 339 Guadecitabine ZINC000043203165 -9 -9 -8.9 -8.97 340 Israpafant ZINC000001533241 -9 -8.9 -8.9 -8.93 341 Derquantel ZINC000056898856 -9 -8.9 -8.9 -8.93 342 Aprepitant ZINC000027428708 -9 -8.9 -8.9 -8.93 343 Saperconazole ZINC000003913989 -9 -8.9 -8.9 -8.93 344 Azd-2014 ZINC000059259288 -8.9 -8.9 -9 -8.93 345 Candesartan ZINC000003782818 -8.9 -8.9 -9 -8.93 346 Delamanid ZINC000043100810 -8.9 -9 -8.9 -8.93 347 Efatutazone ZINC000033975064 -8.8 -8.8 -9.1 -8.90 348 Setipiprant ZINC000091291806 -8.9 -8.9 -8.9 -8.90 349 Lusaperidone ZINC000001903948 -8.9 -8.9 -8.9 -8.90 350 Azaftozine ZINC000022462753 -8.9 -8.9 -8.9 -8.90 351 Pimozide ZINC000004175630 -8.9 -8.9 -8.9 -8.90 352 Amsalog ZINC000005461015 -8.9 -8.9 -8.9 -8.90 353 Iti-007 ZINC000141600395 -8.9 -8.9 -8.9 -8.90 354 Grapiprant ZINC000038228051 -8.9 -8.9 -8.9 -8.90 355 Radezolid ZINC000040379938 -8.9 -8.9 -8.9 -8.90 356 Picloxydine ZINC000030691566 -8.9 -8.9 -8.9 -8.90 357 alpha_Ergocryptine ZINC000575417835 -8.9 -8.9 -8.9 -8.90 358 Afacifenacin ZINC000003991067 -8.9 -8.9 -8.9 -8.90 359 Tolnapersine ZINC000000000792 -8.9 -8.9 -8.9 -8.90 360 Capromorelin ZINC000004393135 -8.9 -8.9 -8.9 -8.90 361 Duoperone ZINC000004215745 -8.9 -8.9 -8.9 -8.90 362 Tanzisertib ZINC000100285204 -8.9 -8.9 -8.9 -8.90 363 Epicriptine ZINC000004215812 -8.9 -8.9 -8.9 -8.90 364 Troglitazone ZINC000000968279 -8.9 -8.9 -8.9 -8.90 365 Etoposide-phosphate ZINC000575418369 -8.9 -8.9 -8.9 -8.90 366 Fiboflapon ZINC000068247071 -8.9 -8.9 -8.9 -8.90 367 Abt-102 ZINC000028964595 -8.9 -8.9 -8.9 -8.90 368 Xl-228 ZINC000203005669 -8.9 -8.9 -8.9 -8.90 369 Masitinib ZINC000034177219 -8.9 -8.9 -8.9 -8.90 370 Etoposide-phosphate ZINC000245205034 -8.9 -8.9 -8.9 -8.90 371 Amg-517 ZINC000014974132 -8.9 -8.9 -8.9 -8.90 372 Pimobendan ZINC000005071680 -8.9 -8.9 -8.9 -8.90 373 Prazosin ZINC000095616601 -8.9 -8.9 -8.9 -8.90 374 Tiospirone ZINC000001915508 -8.9 -8.9 -8.9 -8.90 375 Tadalafil ZINC000008204637 -8.9 -8.9 -8.9 -8.90 376 Temsavir ZINC000034815611 -8.9 -8.9 -8.9 -8.90 377 Gsk239512 ZINC000003961802 -8.9 -8.9 -8.9 -8.90 378 Pratosartan ZINC000003786304 -8.9 -8.9 -8.9 -8.90 379 Guadecitabine ZINC000100285212 -8.9 -8.9 -8.9 -8.90 380 Falecalcitriol ZINC000004474583 -8.9 -8.9 -8.9 -8.90 381 Balaglitazone ZINC000001489816 -8.9 -8.9 -8.9 -8.90 382 Mozavaptan ZINC000006071859 -8.9 -8.9 -8.9 -8.90 383 Ponazuril ZINC000033854754 -8.9 -8.9 -8.9 -8.90 384 Teneligliptin ZINC000036520254 -8.9 -8.9 -8.9 -8.90 385 Minalrestat ZINC000000597385 -8.9 -8.9 -8.9 -8.90 386 Pranazepide ZINC000003798924 -8.9 -8.9 -8.9 -8.90 387 Nafiverine ZINC000072266772 -8.9 -9 -8.8 -8.90 388 Tamatinib ZINC000006745792 -9.1 -8.8 -8.8 -8.90 389 Guadecitabine ZINC000100285210 -9 -8.9 -8.8 -8.90 390 Pamaqueside ZINC000257972190 -9.3 -9.3 -8.1 -8.90 391 Sodelglitazar ZINC000001553281 -8.8 -8.9 -8.9 -8.87 392 Gs-9667 ZINC000256680330 -8.9 -8.8 -8.9 -8.87 393 Sarolaner ZINC000103297729 -8.8 -8.9 -8.9 -8.87 394 Tulopafant ZINC000002016001 -8.9 -8.8 -8.9 -8.87 395 Itraconazole ZINC000003830973 -8.9 -8.8 -8.9 -8.87 396 Dofequidar ZINC000026180140 -8.9 -8.8 -8.9 -8.87 397 Cabotegravir ZINC000096927633 -8.8 -8.9 -8.9 -8.87 398 Saperconazole ZINC000028712570 -8.9 -8.8 -8.9 -8.87 399 beta_Ergocryptine ZINC000100071818 -8.9 -8.8 -8.9 -8.87 400 Tedizolid-phosphate ZINC000043100953 -8.9 -8.9 -8.8 -8.87 401 Elziverine ZINC000072266916 -8.9 -8.9 -8.8 -8.87 402 Amg-548 ZINC000073336080 -8.9 -8.9 -8.8 -8.87 403 Edaglitazone ZINC000001483899 -8.9 -8.9 -8.8 -8.87 404 Sulfamazone ZINC000004194719 -9.1 -8.7 -8.8 -8.87 405 Biriperone ZINC000019366609 -8.9 -8.9 -8.8 -8.87 406 Tropesin ZINC000000638627 -8.8 -9 -8.8 -8.87 407 Tezacaftor ZINC000068206930 -9.1 -8.8 -8.7 -8.87 408 Napitane ZINC000000005009 -8.9 -8.6 -9 -8.83 409 Ecopladib ZINC000085536974 -8.7 -8.9 -8.9 -8.83 410 Darglitazone ZINC000001851105 -8.8 -8.8 -8.9 -8.83 411 Trecadrine ZINC000005751639 -8.8 -8.8 -8.9 -8.83 412 Iti-007 ZINC000143595671 -8.7 -8.9 -8.9 -8.83 413 Yohimbic-acid ZINC000009214629 -8.8 -8.9 -8.8 -8.83 414 Sgx-523 ZINC000039129916 -8.8 -8.9 -8.8 -8.83 415 Lorpiprazole ZINC000033827894 -8.9 -8.8 -8.8 -8.83 416 Talniflumate ZINC000000601275 -8.9 -8.8 -8.8 -8.83 417 Tesevatinib ZINC000117147301 -8.9 -8.8 -8.8 -8.83 418 Saperconazole ZINC000026168046 -8.9 -8.8 -8.8 -8.83 419 Filgotinib ZINC000096174616 -8.9 -8.9 -8.7 -8.83 420 Mizolastine ZINC000013831810 -8.8 -8.8 -8.8 -8.80 421 Spiroxatrine ZINC000053113560 -8.8 -8.8 -8.8 -8.80 422 Etoposide-phosphate ZINC000072186776 -8.8 -8.8 -8.8 -8.80 423 Cc-401 ZINC000038836256 -8.8 -8.8 -8.8 -8.80 424 Etoposide-phosphate ZINC000618072473 -8.8 -8.8 -8.8 -8.80 425 Azaclorzine ZINC000019804668 -8.8 -8.8 -8.8 -8.80 426 Imatinib ZINC000019632618 -8.8 -8.8 -8.8 -8.80 427 Cort-108297 ZINC000029128012 -8.8 -8.8 -8.8 -8.80 428 Vesnarinone ZINC000003781942 -8.8 -8.8 -8.8 -8.80 429 Lirequinil ZINC000003784128 -8.8 -8.8 -8.8 -8.80 430 Quizartinib ZINC000043204002 -8.8 -8.8 -8.8 -8.80 431 Saredutant ZINC000003927605 -8.8 -8.8 -8.8 -8.80 432 Mocetinostat ZINC000013986811 -8.8 -8.8 -8.8 -8.80 433 Danusertib ZINC000006718723 -8.8 -8.8 -8.8 -8.80 434 Riociguat ZINC000003819392 -8.8 -8.8 -8.8 -8.80 435 Metoquizine ZINC000038424542 -8.8 -8.8 -8.8 -8.80 436 Etoposide-phosphate ZINC000306146642 -8.8 -8.8 -8.8 -8.80 437 Osi-930 ZINC000003962535 -8.8 -8.8 -8.8 -8.80 438 Cinprazole ZINC000022463155 -8.8 -8.8 -8.8 -8.80 439 Mozavaptan ZINC000003804565 -8.8 -8.8 -8.8 -8.80 440 Dilmapimod ZINC000034997404 -8.8 -8.8 -8.8 -8.80 441 Glucametacin ZINC000080060444 -8.8 -8.8 -8.8 -8.80 442 Sonepiprazole ZINC000003812548 -8.8 -8.8 -8.8 -8.80 443 Proscillaridin ZINC000257488917 -8.8 -8.8 -8.8 -8.80 444 Pevonedistat ZINC000058660702 -8.8 -8.8 -8.8 -8.80 445 Azd1386 ZINC000139948300 -8.8 -8.8 -8.8 -8.80 446 Varlitinib ZINC000013980035 -8.8 -8.8 -8.8 -8.80 447 Proscillaridin ZINC000306121903 -8.8 -8.8 -8.8 -8.80 448 Etoposide ZINC000003925951 -8.8 -8.8 -8.8 -8.80 449 Azd1386 ZINC000139948444 -8.8 -8.8 -8.8 -8.80 450 Tiplasinin ZINC000003938676 -8.8 -8.8 -8.8 -8.80 451 Glucametacin ZINC000110343950 -8.8 -8.8 -8.8 -8.80 452 Fostemsavir ZINC000014210883 -8.8 -8.8 -8.8 -8.80 453 Etoposide ZINC000011615742 -8.8 -8.8 -8.8 -8.80 454 Metrenperone ZINC000000537997 -8.8 -8.8 -8.8 -8.80 455 Tecovirimat ZINC000035323125 -8.8 -8.8 -8.8 -8.80 456 Tg-02 ZINC000068251500 -8.8 -8.8 -8.8 -8.80 457 Axamozide ZINC000006117407 -8.8 -8.8 -8.8 -8.80 458 Navitoclax ZINC000150338726 -8.3 -9.3 -8.8 -8.80 459 Telmisartan ZINC000001530886 -8.8 -8.8 -8.8 -8.80 460 Proscillaridin ZINC000257488918 -8.8 -8.8 -8.8 -8.80 461 Yohimbic-acid ZINC000005223909 -8.8 -8.8 -8.8 -8.80 462 Etoposide-phosphate ZINC000575418371 -9.3 -8.5 -8.6 -8.80 463 Mitratapide ZINC000003946578 -8.4 -9 -9 -8.80 464 Ci-988 ZINC000014952325 -8.9 -8.7 -8.8 -8.80 465 Monatepil ZINC000001851142 -8.7 -9 -8.7 -8.80 466 Glisamuride ZINC000000537797 -8.3 -8.9 -9.1 -8.77 467 Dirlotapide ZINC000003988502 -8.7 -8.7 -8.9 -8.77 468 Camicinal ZINC000034850365 -8.5 -8.9 -8.9 -8.77 469 Batefenterol ZINC000096941866 -8.7 -8.7 -8.9 -8.77 470 Proscillaridin ZINC000257488916 -8.8 -8.7 -8.8 -8.77 471 alpha_Ergocryptine ZINC000017654092 -8.7 -8.8 -8.8 -8.77 472 Azd-2014 ZINC000059259287 -8.7 -8.8 -8.8 -8.77 473 Tesevatinib ZINC000101781468 -8.8 -8.7 -8.8 -8.77 474 Posaconazole ZINC000011616816 -8.8 -8.7 -8.8 -8.77 475 Draflazine ZINC000022447482 -8.7 -8.8 -8.8 -8.77 476 Pimobendan ZINC000004170129 -8.8 -8.7 -8.8 -8.77 477 Carpipramine ZINC000000597537 -8.7 -8.8 -8.8 -8.77 478 Paliperidone ZINC000001481956 -8.7 -8.9 -8.7 -8.77 479 Tesevatinib ZINC000038912363 -8.8 -8.8 -8.7 -8.77 480 Lapatinib ZINC000001550477 -8.8 -8.8 -8.7 -8.77 481 Glucametacin ZINC000097974785 -8.8 -8.8 -8.7 -8.77 482 Draflazine ZINC000022851754 -8.8 -8.8 -8.7 -8.77 483 Lopinavir ZINC000110906785 -8.8 -8.8 -8.7 -8.77 484 Azd-8055 ZINC000115586131 -8.8 -8.9 -8.6 -8.77 485 Clocapramine ZINC000000608266 -8.9 -8.9 -8.5 -8.77 486 Bi-2536 ZINC000035851315 -8.9 -8.9 -8.5 -8.77 487 Fostamatinib ZINC000043131420 -8.6 -8.6 -9 -8.73 488 Proscillaridin ZINC000306121902 -8.9 -8.4 -8.9 -8.73 489 Aee-788 ZINC000033196300 -8.5 -8.8 -8.9 -8.73 490 Asp-3026 ZINC000068120928 -8.8 -8.5 -8.9 -8.73 491 Palbociclib ZINC000003938686 -8.8 -8.6 -8.8 -8.73 492 Nicodicodine ZINC000004217090 -8.7 -8.7 -8.8 -8.73 493 Itraconazole ZINC000003830974 -8.7 -8.7 -8.8 -8.73 494 Doconazole ZINC000013207499 -8.7 -8.7 -8.8 -8.73 495 Itraconazole ZINC000003830975 -8.7 -8.7 -8.8 -8.73 496 Abamectin-component-b1a ZINC000242649030 -8.8 -8.7 -8.7 -8.73 497 Ritonavir ZINC000040163374 -8.7 -8.8 -8.7 -8.73 498 Sertindole ZINC000000538337 -8.7 -8.8 -8.7 -8.73 499 Tozasertib ZINC000003820040 -9.3 -8.3 -8.6 -8.73 500 Ci-988 ZINC000003920670 -8.8 -8.8 -8.6 -8.73 501 Fluralaner ZINC000095598448 -8.6 -8.7 -8.8 -8.70 502 Zolasartan ZINC000001552379 -8.4 -9.2 -8.5 -8.70 503 Posaconazole ZINC000060392780 -8.7 -8.6 -8.8 -8.70 504 Cabozantinib ZINC000070466416 -8.7 -8.6 -8.8 -8.70 505 Teniposide ZINC000201698152 -8.7 -8.7 -8.7 -8.70 506 Cinuperone ZINC000031425112 -8.7 -8.7 -8.7 -8.70 507 Mk-8033 ZINC000068203670 -8.7 -8.7 -8.7 -8.70 508 Flupentixol ZINC000029489118 -8.7 -8.7 -8.7 -8.70 509 Deserpidine ZINC000105090645 -8.7 -8.7 -8.7 -8.70 510 Etoposide-phosphate ZINC000575418370 -8.7 -8.7 -8.7 -8.70 511 Gs-9667 ZINC000115619865 -8.7 -8.7 -8.7 -8.70 512 Troquidazole ZINC000005422165 -8.7 -8.7 -8.7 -8.70 513 Meribendan ZINC000100378342 -8.7 -8.7 -8.7 -8.70 514 Taniplon ZINC000000010613 -8.7 -8.7 -8.7 -8.70 515 Abt-107 ZINC000038304971 -8.7 -8.7 -8.7 -8.70 516 Tozadenant ZINC000013986943 -8.7 -8.7 -8.7 -8.70 517 Clopipazan ZINC000000001197 -8.7 -8.7 -8.7 -8.70 518 Proscillaridin ZINC000056897526 -8.7 -8.7 -8.7 -8.70 519 Imidocarb ZINC000000073661 -8.7 -8.7 -8.7 -8.70 520 Domperidone ZINC000004175569 -8.7 -8.7 -8.7 -8.70 521 Eperezolid ZINC000003813328 -8.7 -8.7 -8.7 -8.70 522 Bisantrene ZINC000001577736 -8.7 -8.7 -8.7 -8.70 523 Vorapaxar ZINC000003925861 -8.8 -8.6 -8.7 -8.70 524 Toquizine ZINC000000608107 -8.7 -8.7 -8.7 -8.70 525 Rebamipide ZINC000009330879 -8.7 -8.7 -8.7 -8.70 526 Flufylline ZINC000000537738 -8.7 -8.7 -8.7 -8.70 527 Bepafant ZINC000002016003 -8.7 -8.7 -8.7 -8.70 528 Posaconazole ZINC000028639340 -8.7 -8.7 -8.7 -8.70 529 Indisetron ZINC000100102461 -8.7 -8.7 -8.7 -8.70 530 Yohimbic-acid ZINC000000000847 -8.7 -8.7 -8.7 -8.70 531 Elopiprazole ZINC000053098495 -8.7 -8.7 -8.7 -8.70 532 Tak-960 ZINC000043203898 -8.7 -8.7 -8.7 -8.70 533 Itraconazole ZINC000003830976 -8.7 -8.7 -8.7 -8.70 534 Gdc-0994 ZINC000144904566 -8.7 -8.7 -8.7 -8.70 535 Diflomotecan ZINC000001489193 -8.7 -8.7 -8.7 -8.70 536 Heliomycin ZINC000100150837 -8.7 -8.7 -8.7 -8.70 537 Meribendan ZINC000100378338 -8.7 -8.7 -8.7 -8.70 538 Ketoconazole ZINC000000643143 -8.7 -8.7 -8.7 -8.70 539 Etoposide-phosphate ZINC000245205035 -8.7 -8.7 -8.7 -8.70 540 Tebuquine ZINC000001585700 -8.7 -8.7 -8.7 -8.70 541 Terazosin ZINC000095616600 -8.7 -8.7 -8.7 -8.70 542 Drinabant ZINC000059299699 -8.7 -8.7 -8.7 -8.70 543 Glyburide ZINC000000537805 -8.7 -8.7 -8.7 -8.70 544 Amg-548 ZINC000013982572 -8.7 -8.7 -8.7 -8.70 545 Ilorasertib ZINC000063298074 -8.7 -8.7 -8.7 -8.70 546 Iti-007 ZINC000137099035 -8.8 -8.7 -8.6 -8.70 547 Tropesin ZINC000000638630 -8.8 -8.7 -8.6 -8.70 548 Edoxaban ZINC000043200832 -8.4 -8.8 -8.8 -8.67 549 Indinavir ZINC000022448696 -8.7 -8.6 -8.7 -8.67 550 Niceverine ZINC000001481885 -8.7 -8.6 -8.7 -8.67 551 Flutroline ZINC000049590112 -8.7 -8.6 -8.7 -8.67 552 Pf-562271 ZINC000034638188 -8.6 -8.7 -8.7 -8.67 553 Enasidenib ZINC000222731806 -8.7 -8.6 -8.7 -8.67 554 Fluspiperone ZINC000000537753 -8.6 -8.7 -8.7 -8.67 555 Brecanavir ZINC000003994828 -8.7 -8.7 -8.6 -8.67 556 Sulfamazone ZINC000005502399 -8.7 -8.7 -8.6 -8.67 557 Pralnacasan ZINC000003994903 -8.7 -8.7 -8.6 -8.67 558 Brigatinib ZINC000148723177 -8.7 -8.7 -8.6 -8.67 559 Barasertib ZINC000043129461 -8.6 -8.9 -8.5 -8.67 560 Glicaramide ZINC000004216401 -8.6 -8.9 -8.5 -8.67 561 Ensaculin ZINC000001540003 -8.8 -8.7 -8.4 -8.63 562 Sepimostat ZINC000003778392 -8.6 -8.6 -8.7 -8.63 563 Flotrenizine ZINC000031597122 -8.6 -8.6 -8.7 -8.63 564 Fasitibant ZINC000095606973 -8.4 -8.8 -8.7 -8.63 565 Ivarimod ZINC000004216671 -8.5 -8.7 -8.7 -8.63 566 Revizinone ZINC000000538290 -8.6 -8.6 -8.7 -8.63 567 Ketanserin ZINC000000537877 -8.5 -8.7 -8.7 -8.63 568 Posaconazole ZINC000060392778 -8.7 -8.5 -8.7 -8.63 569 Gs-6201 ZINC000029055563 -8.6 -8.6 -8.7 -8.63 570 Int131 ZINC000006485945 -8.6 -8.6 -8.7 -8.63 571 Tesevatinib ZINC000117147304 -8.6 -8.6 -8.7 -8.63 572 Darifenacin ZINC000001996117 -8.6 -8.7 -8.6 -8.63 573 Butanserin ZINC000002019989 -8.6 -8.7 -8.6 -8.63 574 Dabigatran ZINC000001910616 -8.7 -8.6 -8.6 -8.63 575 Etoposide-phosphate ZINC000072186775 -8.6 -8.7 -8.6 -8.63 576 Linarotene ZINC000003927341 -8.7 -8.6 -8.6 -8.63 577 Nafamostat ZINC000003874467 -8.7 -8.6 -8.6 -8.63 578 Granisetron ZINC000000000347 -8.6 -8.7 -8.6 -8.63 579 Pf-03758309 ZINC000222637955 -8.6 -8.7 -8.6 -8.63 580 Ci-988 ZINC000014952331 -8.5 -9 -8.4 -8.63 581 Glucametacin ZINC000080060453 -8.5 -8.6 -8.7 -8.60 582 Seperidol ZINC000000538335 -8.7 -8.4 -8.7 -8.60 583 Posaconazole ZINC000220105129 -8.4 -8.7 -8.7 -8.60 584 Posaconazole ZINC000060392777 -8.6 -8.5 -8.7 -8.60 585 Ci-988 ZINC000014952320 -8.5 -8.6 -8.7 -8.60 586 Argatroban ZINC000003917722 -8.6 -8.6 -8.6 -8.60 587 Funapide ZINC000113473394 -8.6 -8.6 -8.6 -8.60 588 Azd-4547 ZINC000091352092 -8.6 -8.6 -8.6 -8.60 589 Etoposide ZINC000003938684 -8.6 -8.6 -8.6 -8.60 590 Piketoprofen ZINC000000000623 -8.6 -8.6 -8.6 -8.60 591 Delafloxacin ZINC000003827556 -8.6 -8.6 -8.6 -8.60 592 Etoposide-phosphate ZINC000003920020 -8.6 -8.6 -8.6 -8.60 593 Fluralaner ZINC000095598447 -8.6 -8.6 -8.6 -8.60 594 Pimetacin ZINC000000608025 -8.6 -8.6 -8.6 -8.60 595 Teflutixol ZINC000019367492 -8.6 -8.6 -8.6 -8.60 596 Teniposide ZINC000003831509 -8.6 -8.6 -8.6 -8.60 597 Maxacalcitol ZINC000004474617 -8.6 -8.6 -8.6 -8.60 598 Iti-007 ZINC000116262036 -8.5 -8.7 -8.6 -8.60 599 Lidorestat ZINC000000538652 -8.6 -8.6 -8.6 -8.60 600 Troglitazone ZINC000000968277 -8.6 -8.6 -8.6 -8.60 601 Enpiroline ZINC000001568036 -8.6 -8.6 -8.6 -8.60 602 Teniposide ZINC000049605897 -8.6 -8.6 -8.6 -8.60 603 Bagrosin ZINC000026663179 -8.6 -8.6 -8.6 -8.60 604 Etoposide-phosphate ZINC000618072475 -8.6 -8.6 -8.6 -8.60 605 Glisoxepide ZINC000000537804 -8.5 -8.7 -8.6 -8.60 606 Sarizotan ZINC000000021067 -8.6 -8.6 -8.6 -8.60 607 Deserpidine ZINC000003830663 -8.6 -8.6 -8.6 -8.60 608 Toltrazuril ZINC000000538476 -8.6 -8.6 -8.6 -8.60 609 Chlorthalidone ZINC000000020253 -8.6 -8.6 -8.6 -8.60 610 Polydatin ZINC000012888727 -8.6 -8.6 -8.6 -8.60 611 Bagrosin ZINC000026663185 -8.6 -8.6 -8.6 -8.60 612 Sgi-1776 ZINC000068205235 -8.6 -8.6 -8.6 -8.60 613 Bms-777607 ZINC000039716080 -8.6 -8.6 -8.6 -8.60 614 Tiodazosin ZINC000001846466 -8.6 -8.6 -8.6 -8.60 615 ipragliflozin ZINC000306122899 -8.6 -8.6 -8.6 -8.60 616 Mln-2480 ZINC000043202464 -8.6 -8.6 -8.6 -8.60 617 Etoposide ZINC000043648995 -8.6 -8.6 -8.6 -8.60 618 Abt-102 ZINC000028964600 -8.6 -8.6 -8.6 -8.60 619 Birinapant ZINC000096941868 -8.6 -8.6 -8.6 -8.60 620 Etoposide ZINC000003925948 -8.6 -8.6 -8.6 -8.60 621 Teniposide ZINC000003984009 -8.6 -8.6 -8.6 -8.60 622 Saperconazole ZINC000163773658 -8.6 -8.6 -8.6 -8.60 623 Androisoxazole ZINC000013640952 -8.6 -8.6 -8.6 -8.60 624 ipragliflozin ZINC000306122898 -8.6 -8.6 -8.6 -8.60 625 Verecimon ZINC000038562120 -8.6 -8.6 -8.6 -8.60 626 Glipizide ZINC000000537795 -8.6 -8.6 -8.6 -8.60 627 Sb-649868 ZINC000043207236 -8.6 -8.6 -8.6 -8.60 628 Taprizosin ZINC000029042296 -8.6 -8.6 -8.6 -8.60 629 Deserpidine ZINC000003830660 -8.6 -8.6 -8.6 -8.60 630 Gs-9667 ZINC000256680332 -8.6 -8.6 -8.6 -8.60 631 Sulindac ZINC000031356637 -8.6 -8.6 -8.6 -8.60 632 Cinperene ZINC000002018996 -8.6 -8.6 -8.6 -8.60 633 Danitracen ZINC000001481770 -8.6 -8.6 -8.6 -8.60 634 Zanapezil ZINC000000598255 -8.6 -8.6 -8.6 -8.60 635 Enpiroline ZINC000001568034 -8.6 -8.6 -8.6 -8.60 636 Toreforant ZINC000043175812 -8.6 -8.6 -8.6 -8.60 637 Acoxatrine ZINC000005196905 -8.6 -8.6 -8.6 -8.60 638 Relcovaptan ZINC000003931527 -8.6 -8.6 -8.6 -8.60 639 Tezacaftor ZINC000113568483 -8.8 -8.5 -8.5 -8.60 640 Burixafor ZINC000140585706 -8.6 -8.7 -8.5 -8.60 641 Cilostazol ZINC000001552174 -8.7 -8.6 -8.5 -8.60 642 Etoposide ZINC000143020573 -9.4 -8.2 -8.2 -8.60 643 Gandotinib ZINC000068245097 -8.6 -8.4 -8.7 -8.57 644 Lubeluzole ZINC000000537944 -8.6 -8.5 -8.6 -8.57 645 Mespiperone ZINC000002572278 -8.6 -8.5 -8.6 -8.57 646 Terazosin ZINC000095616599 -8.6 -8.5 -8.6 -8.57 647 Nesapidil ZINC000026892447 -8.6 -8.5 -8.6 -8.57 648 Teniposide ZINC000150674146 -8.6 -8.5 -8.6 -8.57 649 Defactinib ZINC000103297739 -8.6 -8.5 -8.6 -8.57 650 Lopinavir ZINC000011616287 -8.6 -8.5 -8.6 -8.57 651 Tioclomarol ZINC000030691430 -8.6 -8.5 -8.6 -8.57 652 Merimepodib ZINC000003975663 -8.6 -8.5 -8.6 -8.57 653 Obatoclax ZINC000029052268 -8.6 -8.6 -8.5 -8.57 654 Ketotrexate ZINC000008628601 -8.6 -8.6 -8.5 -8.57 655 Pilaralisib ZINC000100472223 -8.6 -8.6 -8.5 -8.57 656 Binodenoson ZINC000003932652 -8.6 -8.6 -8.5 -8.57 657 Azd-4547 ZINC000095616598 -8.6 -8.6 -8.5 -8.57 658 Gw590735 ZINC000016052349 -8.6 -8.6 -8.5 -8.57 659 Aceperone ZINC000004214717 -8.6 -8.6 -8.5 -8.57 660 Monatepil ZINC000000607979 -8.3 -8.7 -8.7 -8.57 661 Sapitinib ZINC000034587071 -8.5 -8.6 -8.6 -8.57 662 Preladenant ZINC000053006885 -8.3 -8.8 -8.6 -8.57 663 Gsk-461364 ZINC000059715991 -8.5 -8.6 -8.6 -8.57 664 Palosuran ZINC000034375693 -8.5 -8.7 -8.5 -8.57 665 Flumeridone ZINC000000537741 -8.4 -8.4 -8.8 -8.53 666 Bilastine ZINC000003822702 -8.5 -8.5 -8.6 -8.53 667 Etoposide ZINC000011615744 -8.5 -8.5 -8.6 -8.53 668 Posaconazole ZINC000060392779 -8.5 -8.5 -8.6 -8.53 669 Tadalafil ZINC000003993855 -8.5 -8.5 -8.6 -8.53 670 Foretinib ZINC000043204048 -8.6 -8.4 -8.6 -8.53 671 Nebivolol ZINC000004213946 -8.6 -8.4 -8.6 -8.53 672 Reserpine ZINC000003978051 -8.5 -8.5 -8.6 -8.53 673 Rivaroxaban ZINC000001494180 -8.5 -8.5 -8.6 -8.53 674 Solypertine ZINC000004214326 -8.5 -8.5 -8.6 -8.53 675 Dasatinib ZINC000003986735 -8.5 -8.5 -8.6 -8.53 676 Itraconazole ZINC000004097343 -8.5 -8.5 -8.6 -8.53 677 Sitogluside ZINC000253476255 -8.6 -8.5 -8.5 -8.53 678 Peliglitazar ZINC000003935841 -8.5 -8.6 -8.5 -8.53 679 Quiflapon ZINC000001914818 -8.6 -8.5 -8.5 -8.53 680 Piketoprofen ZINC000001846243 -8.5 -8.6 -8.5 -8.53 681 Salazosulfadimidine ZINC000004194759 -8.6 -8.5 -8.5 -8.53 682 Temanogrel ZINC000035920376 -8.5 -8.6 -8.5 -8.53 683 Doramapimod ZINC000024044436 -8.6 -8.5 -8.5 -8.53 684 Deserpidine ZINC000004097186 -8.5 -8.6 -8.5 -8.53 685 Fluprofylline ZINC000000537750 -8.5 -8.6 -8.5 -8.53 686 Tedizolid-phosphate ZINC000117720221 -8.6 -8.5 -8.5 -8.53 687 Bazedoxifene ZINC000001895505 -8.5 -8.6 -8.5 -8.53 688 Glisentide ZINC000000537793 -8.6 -8.5 -8.5 -8.53 689 Sulfaloxic-acid ZINC000002020014 -8.5 -8.6 -8.5 -8.53 690 Saperconazole ZINC000004214295 -8.6 -8.5 -8.5 -8.53 691 Amesergide ZINC000083261402 -8.5 -8.6 -8.5 -8.53 692 Kw-2449 ZINC000043201999 -8.5 -8.6 -8.5 -8.53 693 Tanogitran ZINC000064527030 -8.6 -8.5 -8.5 -8.53 694 Sitogluside ZINC000253534732 -8.8 -8.4 -8.4 -8.53 695 Clazosentan ZINC000003939238 -8.7 -8.5 -8.4 -8.53 696 Etoposide ZINC000011615745 -8.8 -8.4 -8.4 -8.53 697 Volixibat ZINC000164888446 -8.7 -8.7 -8.2 -8.53 698 Lotrafiban ZINC000003812598 -8.1 -8.7 -8.7 -8.50 699 Spiclomazine ZINC000000538363 -8.3 -8.6 -8.6 -8.50 700 Glisolamide ZINC000000537802 -8.4 -8.5 -8.6 -8.50 701 Ilomastat ZINC000003780014 -8.5 -8.5 -8.5 -8.50 702 Lidanserin ZINC000013883416 -8.6 -8.4 -8.5 -8.50 703 Raxatrigine ZINC000113543591 -8.5 -8.5 -8.5 -8.50 704 Ambruticin ZINC000008214482 -8.5 -8.5 -8.5 -8.50 705 Mimbane ZINC000004213866 -8.5 -8.5 -8.5 -8.50 706 Acolbifene ZINC000000598598 -8.6 -8.4 -8.5 -8.50 707 Z160 ZINC000020509316 -8.5 -8.5 -8.5 -8.50 708 Napitane ZINC000005934263 -8.5 -8.5 -8.5 -8.50 709 Saperconazole ZINC000028712571 -8.5 -8.5 -8.5 -8.50 710 Lombazole ZINC000004213681 -8.5 -8.5 -8.5 -8.50 711 Rucaparib ZINC000000025958 -8.5 -8.5 -8.5 -8.50 712 Tiomergine ZINC000004217573 -8.5 -8.5 -8.5 -8.50 713 Polydatin ZINC000012888734 -8.5 -8.5 -8.5 -8.50 714 Quinaldine-blue ZINC000001687632 -8.5 -8.5 -8.5 -8.50 715 Azelastine ZINC000000897240 -8.5 -8.5 -8.5 -8.50 716 Mk-0893 ZINC000068250425 -8.5 -8.5 -8.5 -8.50 717 Maraviroc ZINC000100003902 -8.5 -8.5 -8.5 -8.50 718 Presatovir ZINC000205657764 -8.5 -8.5 -8.5 -8.50 719 Motesanib ZINC000018710082 -8.5 -8.5 -8.5 -8.50 720 Leq506 ZINC000103298500 -8.5 -8.5 -8.5 -8.50 721 Toquizine ZINC000002029587 -8.5 -8.5 -8.5 -8.50 722 Polydatin ZINC000012888715 -8.5 -8.5 -8.5 -8.50 723 Oxycinchophen ZINC000000001877 -8.5 -8.5 -8.5 -8.50 724 Flunitrazepam ZINC000003812994 -8.5 -8.5 -8.5 -8.50 725 Lirimilast ZINC000001547848 -8.5 -8.5 -8.5 -8.50 726 Glucametacin ZINC000110343953 -8.5 -8.5 -8.5 -8.50 727 Eletriptan ZINC000003823475 -8.5 -8.5 -8.5 -8.50 728 Hoquizil ZINC000000537831 -8.5 -8.5 -8.5 -8.50 729 Glucametacin ZINC000097974783 -8.5 -8.5 -8.5 -8.50 730 Sitaxentan ZINC000001481831 -8.5 -8.5 -8.5 -8.50 731 Lasmiditan ZINC000003818355 -8.5 -8.5 -8.5 -8.50 732 Cloperidone ZINC000004215426 -8.5 -8.5 -8.5 -8.50 733 Nifuroquine ZINC000001842848 -8.5 -8.5 -8.5 -8.50 734 Eluxadoline ZINC000014210876 -8.5 -8.5 -8.5 -8.50 735 Ast-487 ZINC000023247639 -8.5 -8.5 -8.5 -8.50 736 Mln-2480 ZINC000043202463 -8.5 -8.5 -8.5 -8.50 737 Lufuradom ZINC000000607947 -8.5 -8.5 -8.5 -8.50 738 Metolazone ZINC000000896755 -8.5 -8.5 -8.5 -8.50 739 Etoposide ZINC000100042690 -8.5 -8.5 -8.5 -8.50 740 Oxametacin ZINC000000608008 -8.5 -8.5 -8.5 -8.50 741 Spiperone ZINC000000643233 -8.5 -8.5 -8.5 -8.50 742 Suvorexant ZINC000049036447 -8.5 -8.5 -8.5 -8.50 743 Azasetron ZINC000002528474 -8.5 -8.5 -8.5 -8.50 744 Gsk-1070916 ZINC000043170519 -8.5 -8.5 -8.5 -8.50 745 Proscillaridin ZINC000008214665 -8.5 -8.5 -8.5 -8.50 746 Lucitanib ZINC000077024213 -8.5 -8.5 -8.5 -8.50 747 Taziprinone ZINC000022463338 -8.5 -8.5 -8.5 -8.50 748 Gs-9667 ZINC000256680333 -8.5 -8.5 -8.5 -8.50 749 Tilmacoxib ZINC000000006662 -8.5 -8.5 -8.5 -8.50 750 Rilopirox ZINC000000538303 -8.5 -8.5 -8.5 -8.50 751 Zopolrestat ZINC000000538557 -8.5 -8.5 -8.5 -8.50 752 Folic-acid ZINC000008577218 -8.5 -8.5 -8.5 -8.50 753 Teniposide ZINC000003831508 -8.5 -8.5 -8.5 -8.50 754 Syrosingopine ZINC000004214363 -8.5 -8.5 -8.5 -8.50 755 Copanlisib ZINC000068247389 -8.5 -8.5 -8.5 -8.50 756 Tofogliflozin ZINC000035826342 -8.5 -8.5 -8.5 -8.50 757 Evacetrapib ZINC000150338934 -8.5 -8.5 -8.5 -8.50 758 Olodaterol ZINC000034636383 -8.5 -8.5 -8.5 -8.50 759 Argatroban ZINC000003807172 -8.5 -8.5 -8.5 -8.50 760 Aprepitant ZINC000052245742 -8.5 -8.5 -8.5 -8.50 761 Apixaban ZINC000011677837 -8.5 -8.5 -8.5 -8.50 762 Pholcodine ZINC000004217287 -8.5 -8.5 -8.5 -8.50 763 Gdc-0994 ZINC000144904353 -8.5 -8.5 -8.5 -8.50 764 Sopitazine ZINC000000538361 -8.5 -8.5 -8.5 -8.50 765 Presatovir ZINC000147513579 -8.5 -8.5 -8.5 -8.50 766 Desocriptine ZINC000004212849 -8.5 -8.5 -8.5 -8.50 767 Moexiprilat ZINC000003789196 -8.5 -8.6 -8.4 -8.50 768 Trifluperidol ZINC000000538505 -8.7 -8.5 -8.3 -8.50 769 Deserpidine ZINC000003830661 -8.6 -8.7 -8.2 -8.50 770 Nafiverine ZINC000022463090 -8.4 -8.2 -8.8 -8.47 771 Razaxaban ZINC000003633839 -8.4 -8.4 -8.6 -8.47 772 Teniposide ZINC000254077833 -8.5 -8.3 -8.6 -8.47 773 Fedratinib ZINC000019862646 -8.4 -8.4 -8.6 -8.47 774 Docetaxel ZINC000085537053 -8.6 -8.2 -8.6 -8.47 775 Vidupiprant ZINC000043206238 -8.5 -8.4 -8.5 -8.47 776 Fuprazole ZINC000022463197 -8.4 -8.5 -8.5 -8.47 777 Ftormetazine ZINC000019338440 -8.4 -8.5 -8.5 -8.47 778 Salazodine ZINC000003917759 -8.5 -8.4 -8.5 -8.47 779 Nicofuranose ZINC000004217093 -8.5 -8.4 -8.5 -8.47 780 Flutroline ZINC000049590110 -8.5 -8.4 -8.5 -8.47 781 Itraconazole ZINC000004097344 -8.5 -8.4 -8.5 -8.47 782 Ecenofloxacin ZINC000031495028 -8.5 -8.4 -8.5 -8.47 783 Bentiromide ZINC000000608204 -8.5 -8.4 -8.5 -8.47 784 Polydatin ZINC000021983181 -8.5 -8.5 -8.4 -8.47 785 Perbufylline ZINC000033852267 -8.5 -8.5 -8.4 -8.47 786 Perospirone ZINC000013828184 -8.5 -8.5 -8.4 -8.47 787 Nesapidil ZINC000026892453 -8.5 -8.5 -8.4 -8.47 788 Fasiglifam ZINC000068208039 -8.5 -8.5 -8.4 -8.47 789 Olmesartan_medoxomil ZINC000004149248 -8.5 -8.5 -8.4 -8.47 790 Azd2066 ZINC000034885049 -8.5 -8.5 -8.4 -8.47 791 Alpelisib ZINC000068198368 -8.5 -8.5 -8.4 -8.47 792 Azd-4547 ZINC000091352093 -8.5 -8.5 -8.4 -8.47 793 Asunaprevir ZINC000085540202 -8.5 -8.5 -8.4 -8.47 794 Diosmetin ZINC000005733652 -8.5 -8.5 -8.4 -8.47 795 Neflumozide ZINC000000538067 -8.9 -8.2 -8.3 -8.47 796 Repirinast ZINC000000538285 -8.7 -8.6 -8.1 -8.47 797 Niraparib ZINC000043206370 -8.3 -8.4 -8.6 -8.43 798 Ketotrexate ZINC000008628600 -8.5 -8.3 -8.5 -8.43 799 Abitesartan ZINC000003806120 -8.3 -8.5 -8.5 -8.43 800 Dagrocorat ZINC000103297733 -8.5 -8.4 -8.4 -8.43 801 Cp-724714 ZINC000018710086 -8.5 -8.4 -8.4 -8.43 802 Ketoconazole ZINC000000643153 -8.5 -8.4 -8.4 -8.43 803 Besonprodil ZINC000027299440 -8.5 -8.4 -8.4 -8.43 804 Panamesine ZINC000003801505 -8.5 -8.4 -8.4 -8.43 805 Canagliflozin ZINC000043207238 -8.4 -8.4 -8.5 -8.43 806 Sabeluzole ZINC000004214288 -8.4 -8.4 -8.5 -8.43 807 Ticagrelor ZINC000150295908 -8.4 -8.4 -8.5 -8.43 808 Terconazole ZINC000003873934 -8.4 -8.5 -8.4 -8.43 809 Sabeluzole ZINC000001999437 -8.4 -8.5 -8.4 -8.43 810 Rivoglitazone ZINC000001481958 -8.4 -8.5 -8.4 -8.43 811 Terconazole ZINC000003873936 -8.4 -8.6 -8.3 -8.43 812 Nicofurate ZINC000072266769 -8.5 -8.6 -8.2 -8.43 813 Lidoflazine ZINC000022034381 -8.5 -8.6 -8.2 -8.43 814 Osanetant ZINC000003935475 -8.5 -8.6 -8.2 -8.43 815 Naxaprostene ZINC000004217054 -8.2 -8.2 -8.8 -8.40 816 Trabodenoson ZINC000214055339 -8.2 -8.5 -8.5 -8.40 817 Umespirone ZINC000003781315 -8.3 -8.4 -8.5 -8.40 818 Ketoconazole ZINC000000643138 -8.4 -8.3 -8.5 -8.40 819 Tipentosin ZINC000002014160 -8.4 -8.4 -8.4 -8.40 820 Nefazodone ZINC000000538065 -8.4 -8.4 -8.4 -8.40 821 Apitolisib ZINC000059224388 -8.4 -8.4 -8.4 -8.40 822 Sulindac-sulfone ZINC000013531944 -8.4 -8.4 -8.4 -8.40 823 Folic-acid ZINC000008585850 -8.4 -8.4 -8.4 -8.40 824 Ketoconazole ZINC000003872994 -8.4 -8.4 -8.4 -8.40 825 Tg-02 ZINC000095938323 -8.4 -8.4 -8.4 -8.40 826 Flezelastine ZINC000003785445 -8.4 -8.4 -8.4 -8.40 827 Sitogluside ZINC000253609312 -8.4 -8.4 -8.4 -8.40 828 ipragliflozin ZINC000165806177 -8.4 -8.4 -8.4 -8.40 829 Trabodenoson ZINC000642805871 -8.4 -8.4 -8.4 -8.40 830 Ac-430 ZINC000095079935 -8.4 -8.4 -8.4 -8.40 831 Mesulergine ZINC000004216874 -8.4 -8.4 -8.4 -8.40 832 Etoposide ZINC000079216638 -8.4 -8.4 -8.4 -8.40 833 Vestipitant ZINC000003936035 -8.4 -8.4 -8.4 -8.40 834 Teniposide ZINC000028226553 -8.4 -8.4 -8.4 -8.40 835 Polydatin ZINC000003881960 -8.4 -8.4 -8.4 -8.40 836 Napitane ZINC000003794361 -8.4 -8.4 -8.4 -8.40 837 Mindoperone ZINC000004213869 -8.4 -8.4 -8.4 -8.40 838 Glucametacin ZINC000077293064 -8.3 -8.5 -8.4 -8.40 839 Terfenadine ZINC000003812892 -8.4 -8.4 -8.4 -8.40 840 Netoglitazone ZINC000003633833 -8.4 -8.4 -8.4 -8.40 841 Glucametacin ZINC000575346762 -8.4 -8.4 -8.4 -8.40 842 Dioxadrol ZINC000008143662 -8.4 -8.4 -8.4 -8.40 843 Belotecan ZINC000003826691 -8.4 -8.4 -8.4 -8.40 844 Deserpidine ZINC000257400370 -8.4 -8.4 -8.4 -8.40 845 ipragliflozin ZINC000038897728 -8.4 -8.4 -8.4 -8.40 846 Setiptiline ZINC000001482169 -8.4 -8.4 -8.4 -8.40 847 Clodoxopone ZINC000004215401 -8.4 -8.4 -8.4 -8.40 848 Gimatecan ZINC000003993519 -8.4 -8.4 -8.4 -8.40 849 Terconazole ZINC000000897382 -8.4 -8.4 -8.4 -8.40 850 Quisinostat ZINC000035836133 -8.4 -8.4 -8.4 -8.40 851 Polydatin ZINC000005923201 -8.4 -8.4 -8.4 -8.40 852 Riviciclib ZINC000003937395 -8.4 -8.4 -8.4 -8.40 853 Eleclazine ZINC000206191652 -8.4 -8.4 -8.4 -8.40 854 Edifolone ZINC000004215756 -8.4 -8.4 -8.4 -8.40 855 Nebivolol ZINC000011681534 -8.4 -8.4 -8.4 -8.40 856 Fendizoate ZINC000000001431 -8.4 -8.4 -8.4 -8.40 857 Teniposide ZINC000049605898 -8.4 -8.4 -8.4 -8.40 858 Nantradol ZINC000030691106 -8.4 -8.4 -8.4 -8.40 859 Fluperlapine ZINC000026247473 -8.4 -8.4 -8.4 -8.40 860 alpha_Ergocryptine ZINC000095810539 -8.4 -8.4 -8.4 -8.40 861 Ontazolast ZINC000000005761 -8.4 -8.4 -8.4 -8.40 862 Pirenperone ZINC000000538194 -8.4 -8.4 -8.4 -8.40 863 Imanixil ZINC000000537853 -8.4 -8.4 -8.4 -8.40 864 Taclamine ZINC000001481926 -8.4 -8.4 -8.4 -8.40 865 Tetrazolast ZINC000000004014 -8.4 -8.4 -8.4 -8.40 866 Netoglitazone ZINC000001481955 -8.4 -8.4 -8.4 -8.40 867 Gsk189254 ZINC000003961799 -8.4 -8.4 -8.4 -8.40 868 Aranotin ZINC000004214877 -8.4 -8.4 -8.4 -8.40 869 ipragliflozin ZINC000605694508 -8.4 -8.4 -8.4 -8.40 870 Riviciclib ZINC000113496418 -8.4 -8.4 -8.4 -8.40 871 Mk-2206 ZINC000036382821 -8.4 -8.4 -8.4 -8.40 872 Flortaucipir ZINC000148048492 -8.4 -8.4 -8.4 -8.40 873 Crenolanib ZINC000003820043 -8.4 -8.4 -8.4 -8.40 874 Rg-547 ZINC000013983251 -8.4 -8.4 -8.4 -8.40 875 Tandutinib ZINC000003966243 -8.4 -8.4 -8.4 -8.40 876 Bms-754807 ZINC000145213336 -8.4 -8.4 -8.4 -8.40 877 Cediranib ZINC000003948085 -8.4 -8.4 -8.4 -8.40 878 Enadoline ZINC000001914437 -8.4 -8.4 -8.4 -8.40 879 Bendroflumethiazide ZINC000000601301 -8.4 -8.4 -8.4 -8.40 880 Teniposide ZINC000245190531 -8.4 -8.4 -8.4 -8.40 881 Amsacrine ZINC000003812923 -8.4 -8.4 -8.4 -8.40 882 Nelfinavir ZINC000003833846 -8.4 -8.4 -8.4 -8.40 883 Carsatrin ZINC000022851028 -8.3 -8.5 -8.4 -8.40 884 Furomazine ZINC000003598305 -8.4 -8.4 -8.4 -8.40 885 Pemetrexed ZINC000001851132 -8.5 -8.3 -8.4 -8.40 886 Traxanox ZINC000000002203 -8.4 -8.4 -8.4 -8.40 887 Abamectin-component-b1a ZINC000242649031 -8.4 -8.4 -8.4 -8.40 888 Talmetoprim ZINC000000538405 -8.4 -8.4 -8.4 -8.40 889 Pelanserin ZINC000000538156 -8.4 -8.4 -8.4 -8.40 890 Spiroxatrine ZINC000053113561 -8.4 -8.4 -8.4 -8.40 891 Astemizole ZINC000000601274 -8.5 -8.4 -8.3 -8.40 892 Letaxaban ZINC000013986542 -8.8 -8.2 -8.2 -8.40 893 Frabuprofen ZINC000031555620 -8.7 -8.3 -8.2 -8.40 894 Azilsartan-medoxomil ZINC000014210642 -9 -8.1 -8.1 -8.40 895 Amtolmetin_guacil ZINC000000596929 -8.4 -8.1 -8.6 -8.37 896 Ciltoprazine ZINC000004215333 -8.3 -8.3 -8.5 -8.37 897 Muraglitazar ZINC000049650290 -8.3 -8.3 -8.5 -8.37 898 Veliflapon ZINC000000598193 -8.5 -8.1 -8.5 -8.37 899 Pranlukast ZINC000001542146 -8.4 -8.3 -8.4 -8.37 900 Teniposide ZINC000245190530 -8.4 -8.3 -8.4 -8.37 901 Tioclomarol ZINC000030691425 -8.4 -8.3 -8.4 -8.37 902 Ce-224535 ZINC000034662892 -8.4 -8.3 -8.4 -8.37 903 Setoperone ZINC000000538339 -8.4 -8.3 -8.4 -8.37 904 Cinperene ZINC000002018994 -8.3 -8.4 -8.4 -8.37 905 Cort-108297 ZINC000141514903 -8.4 -8.3 -8.4 -8.37 906 Milenperone ZINC000000538006 -8.3 -8.4 -8.4 -8.37 907 Deserpidine ZINC000257400372 -8.4 -8.3 -8.4 -8.37 908 Valsartan ZINC000003875259 -8.4 -8.3 -8.4 -8.37 909 Ticagrelor ZINC000204935778 -8.3 -8.4 -8.4 -8.37 910 Idenast ZINC000033754357 -8.4 -8.3 -8.4 -8.37 911 Ph-797804 ZINC000013980453 -8.3 -8.4 -8.4 -8.37 912 Nirogacestat ZINC000038217838 -8.4 -8.3 -8.4 -8.37 913 Telotristat ZINC000084758235 -8.3 -8.5 -8.3 -8.37 914 Glibutimine ZINC000031601260 -8.4 -8.4 -8.3 -8.37 915 Deserpidine ZINC000003830662 -8.4 -8.4 -8.3 -8.37 916 Taprenepag ZINC000072266311 -8.4 -8.4 -8.3 -8.37 917 Dapiprazole ZINC000000001246 -8.4 -8.4 -8.3 -8.37 918 Neocinchophen ZINC000000001791 -8.4 -8.4 -8.3 -8.37 919 Sitogluside ZINC000118922613 -8.4 -8.4 -8.3 -8.37 920 Gliflumide ZINC000001481851 -8.3 -8.5 -8.3 -8.37 921 Rivoglitazone ZINC000004214702 -8.4 -8.4 -8.3 -8.37 922 Acodazole ZINC000018009339 -8.5 -8.4 -8.2 -8.37 923 Peraquinsin ZINC000004214134 -8.6 -8.4 -8.1 -8.37 924 Glicetanile ZINC000000607915 -8.2 -8.4 -8.5 -8.37 925 Glunicate ZINC000004216419 -8.7 -8.2 -8.2 -8.37 926 Rilapladib ZINC000003973276 -8.2 -8.8 -8.1 -8.37 927 Talotrexin ZINC000003807186 -8.1 -8.1 -8.8 -8.33 928 Infigratinib ZINC000072105034 -8.3 -8.2 -8.5 -8.33 929 Imiglitazar ZINC000049756486 -8.2 -8.3 -8.5 -8.33 930 ipragliflozin ZINC000165806297 -8.3 -8.3 -8.4 -8.33 931 Sitogluside ZINC000253609314 -8.3 -8.3 -8.4 -8.33 932 Etoposide-phosphate ZINC000245205037 -8.3 -8.3 -8.4 -8.33 933 Oxatomide ZINC000019632896 -8.3 -8.3 -8.4 -8.33 934 Irindalone ZINC000022463226 -8.3 -8.3 -8.4 -8.33 935 Ticagrelor ZINC000605696437 -8.3 -8.3 -8.4 -8.33 936 Gsk-2636771 ZINC000077024226 -8.3 -8.3 -8.4 -8.33 937 Prinomastat ZINC000000580328 -8.3 -8.3 -8.4 -8.33 938 Siguazodan ZINC000003995874 -8.4 -8.3 -8.3 -8.33 939 Imiclopazine ZINC000022463214 -8.3 -8.4 -8.3 -8.33 940 Ce-224535 ZINC000035939968 -8.2 -8.5 -8.3 -8.33 941 Saracatinib ZINC000024811973 -8.4 -8.3 -8.3 -8.33 942 Simetride ZINC000004217449 -8.4 -8.3 -8.3 -8.33 943 Pretomanid ZINC000003821675 -8.3 -8.4 -8.3 -8.33 944 Octrizole ZINC000001849911 -8.3 -8.4 -8.3 -8.33 945 Azimilide ZINC000021983255 -8.3 -8.4 -8.3 -8.33 946 Tamibarotene ZINC000000538415 -8.4 -8.3 -8.3 -8.33 947 Tezosentan ZINC000003954692 -8.4 -8.3 -8.3 -8.33 948 Chloroserpidine ZINC000004212444 -8.4 -8.3 -8.3 -8.33 949 Gosogliptin ZINC000023247686 -8.4 -8.3 -8.3 -8.33 950 Fenflumizole ZINC000000608375 -8.3 -8.4 -8.3 -8.33 951 Quinapril ZINC000003801163 -8.4 -8.3 -8.3 -8.33 952 Mapracorat ZINC000035952535 -8.3 -8.4 -8.3 -8.33 953 Hydrobentizide ZINC000001842993 -8.3 -8.4 -8.3 -8.33 954 Regadenoson ZINC000003598383 -8.4 -8.3 -8.3 -8.33 955 Velpatasvir ZINC000504665933 -8.5 -8.5 -8 -8.33 956 Carsatrin ZINC000022851029 -8.3 -8.3 -8.3 -8.30 957 Draquinolol ZINC000004213051 -8.3 -8.3 -8.3 -8.30 958 Azasetron ZINC000000004132 -8.3 -8.3 -8.3 -8.30 959 Maroxepin ZINC000000001647 -8.3 -8.3 -8.3 -8.30 960 Pf-00446687 ZINC000013983541 -8.3 -8.3 -8.3 -8.30 961 Revaprazan ZINC000003633835 -8.3 -8.3 -8.3 -8.30 962 Azatadine ZINC000000968337 -8.3 -8.3 -8.3 -8.30 963 Tazifylline ZINC000019801842 -8.3 -8.3 -8.3 -8.30 964 Opanixil ZINC000084758648 -8.3 -8.3 -8.3 -8.30 965 Befiradol ZINC000001492397 -8.3 -8.3 -8.3 -8.30 966 Flubendazole ZINC000003830847 -8.3 -8.3 -8.3 -8.30 967 Folitixorin ZINC000004654260 -8.3 -8.3 -8.3 -8.30 968 Olcegepant ZINC000098052868 -8.3 -8.3 -8.3 -8.30 969 ipragliflozin ZINC000669678948 -8.3 -8.3 -8.3 -8.30 970 Zstk-474 ZINC000100683574 -8.3 -8.3 -8.3 -8.30 971 Metiapine ZINC000056897544 -8.3 -8.3 -8.3 -8.30 972 Entinostat ZINC000001488870 -8.3 -8.3 -8.3 -8.30 973 Axitirome ZINC000001538134 -8.3 -8.3 -8.3 -8.30 974 Doconazole ZINC000001567316 -8.3 -8.3 -8.3 -8.30 975 Istradefylline ZINC000003803921 -8.3 -8.3 -8.3 -8.30 976 Calcipotriene ZINC000100489836 -8.3 -8.3 -8.3 -8.30 977 Lombazole ZINC000005425510 -8.3 -8.3 -8.3 -8.30 978 Sonedenoson ZINC000003966398 -8.3 -8.3 -8.3 -8.30 979 Acemetacin ZINC000000601272 -8.3 -8.3 -8.3 -8.30 980 Polydatin ZINC000142857948 -8.3 -8.3 -8.3 -8.30 981 Cebaracetam ZINC000002016005 -8.3 -8.3 -8.3 -8.30 982 Etoposide ZINC000003978071 -8.3 -8.3 -8.3 -8.30 983 Vidarabine-phosphoric-acid ZINC000504744048 -8.3 -8.3 -8.3 -8.30 984 Toquizine ZINC000005317406 -8.3 -8.3 -8.3 -8.30 985 Picumast ZINC000019367677 -8.3 -8.3 -8.3 -8.30 986 Roxoperone ZINC000000002045 -8.3 -8.3 -8.3 -8.30 987 Zibotentan ZINC000001491485 -8.3 -8.3 -8.3 -8.30 988 Pki-166 ZINC000000023255 -8.3 -8.3 -8.3 -8.30 989 Tidembersat ZINC000003823817 -8.3 -8.3 -8.3 -8.30 990 Thiothixene ZINC000030690433 -8.3 -8.3 -8.3 -8.30 991 Aripiprazole ZINC000001851149 -8.3 -8.3 -8.3 -8.30 992 Trimethaphan ZINC000003831581 -8.3 -8.3 -8.3 -8.30 993 Sulisatin ZINC000004217484 -8.3 -8.3 -8.3 -8.30 994 Yohimbic-acid ZINC000003947439 -8.3 -8.3 -8.3 -8.30 995 Mazapertine ZINC000052956332 -8.3 -8.3 -8.3 -8.30 996 Puromycin ZINC000053147179 -8.3 -8.3 -8.3 -8.30 997 Xenazoic-acid ZINC000002044292 -8.3 -8.3 -8.3 -8.30 998 Quinaprilat ZINC000004217387 -8.3 -8.3 -8.3 -8.30 999 Niravoline ZINC000000607401 -8.3 -8.3 -8.3 -8.30 1000 Laprafylline ZINC000022463231 -8.3 -8.3 -8.3 -8.30 1001 Vx-745 ZINC000013493055 -8.3 -8.3 -8.3 -8.30 1002 Spiroglumide ZINC000001554851 -8.3 -8.3 -8.3 -8.30 1003 Amiperone ZINC000004214827 -8.3 -8.3 -8.3 -8.30 1004 Pipendoxifene ZINC000000602799 -8.3 -8.3 -8.3 -8.30 1005 Bedoradrine ZINC000000584203 -8.2 -8.4 -8.3 -8.30 1006 Ranirestat ZINC000000598588 -8.3 -8.3 -8.3 -8.30 1007 Yohimbic-acid ZINC000003947440 -8.3 -8.3 -8.3 -8.30 1008 Midostaurin ZINC000100013130 -8.3 -8.3 -8.3 -8.30 1009 Piflutixol ZINC000031297681 -8.3 -8.3 -8.3 -8.30 1010 Etoposide ZINC000103553211 -8.3 -8.3 -8.3 -8.30 1011 Ansoxetine ZINC000005957953 -8.3 -8.3 -8.3 -8.30 1012 Indapamide ZINC000000601305 -8.3 -8.3 -8.3 -8.30 1013 Leucocianidol ZINC000000968223 -8.3 -8.3 -8.3 -8.30 1014 Oc000459 ZINC000043120334 -8.3 -8.3 -8.3 -8.30 1015 Disulergine ZINC000004215704 -8.3 -8.3 -8.3 -8.30 1016 Nitraquazone ZINC000000001819 -8.3 -8.3 -8.3 -8.30 1017 Polydatin ZINC000003881959 -8.3 -8.3 -8.3 -8.30 1018 Cariprazine ZINC000100153731 -8.3 -8.3 -8.3 -8.30 1019 Tesicam ZINC000002015796 -8.3 -8.3 -8.3 -8.30 1020 Tideglusib ZINC000013985228 -8.3 -8.3 -8.3 -8.30 1021 Benzaprinoxide ZINC000000001009 -8.3 -8.3 -8.3 -8.30 1022 Pyrvinium ZINC000003831401 -8.3 -8.3 -8.3 -8.30 1023 Hydroxyestrone_diacetate ZINC000253492745 -8.3 -8.3 -8.3 -8.30 1024 Cyclocumarol ZINC000002036736 -8.3 -8.3 -8.3 -8.30 1025 Levomefolic-acid ZINC000002005305 -8.3 -8.3 -8.3 -8.30 1026 Ticagrelor ZINC000204935796 -8.1 -8.3 -8.5 -8.30 1027 ipragliflozin ZINC000205605627 -8.4 -8.1 -8.4 -8.30 1028 Raltitrexed ZINC000003832372 -8.4 -8.2 -8.3 -8.30 1029 Glibutimine ZINC000031601255 -8.4 -8.3 -8.2 -8.30 1030 Tak-441 ZINC000043207688 -8.2 -8.5 -8.2 -8.30 1031 Clothixamide ZINC000000608277 -8.2 -8.6 -8.1 -8.30 1032 Proscillaridin ZINC000257355131 -8.7 -8.1 -8.1 -8.30 1033 Brexpiprazole ZINC000084758479 -8.4 -8.4 -8.1 -8.30 1034 Frabuprofen ZINC000004213393 -8.2 -8.2 -8.4 -8.27 1035 Itraconazole ZINC000028007115 -8.2 -8.3 -8.3 -8.27 1036 Indacaterol ZINC000035801098 -8.3 -8.2 -8.3 -8.27 1037 Levomefolic-acid ZINC000002572666 -8.2 -8.3 -8.3 -8.27 1038 Volasertib ZINC000100071772 -8.2 -8.3 -8.3 -8.27 1039 Rivaroxaban ZINC000003964126 -8.2 -8.3 -8.3 -8.27 1040 Terconazole ZINC000003873935 -8.3 -8.2 -8.3 -8.27 1041 Tesicam ZINC000000000749 -8.3 -8.2 -8.3 -8.27 1042 Strychnine ZINC000000119434 -8.3 -8.2 -8.3 -8.27 1043 Mln-0128 ZINC000073069271 -8.2 -8.3 -8.3 -8.27 1044 Gw842166x ZINC000003947932 -8.3 -8.2 -8.3 -8.27 1045 Piclozotan ZINC000001892462 -8.3 -8.2 -8.3 -8.27 1046 Tesevatinib ZINC000114456300 -8.2 -8.3 -8.3 -8.27 1047 Naftopidil ZINC000019632696 -8.2 -8.3 -8.3 -8.27 1048 Tipifarnib ZINC000028473960 -8.2 -8.3 -8.3 -8.27 1049 Bamirastine ZINC000003927238 -8.2 -8.3 -8.3 -8.27 1050 Nifenazone ZINC000000057417 -8.2 -8.3 -8.3 -8.27 1051 Pipamperone ZINC000021297287 -8.2 -8.3 -8.3 -8.27 1052 ipragliflozin ZINC000306122897 -8.3 -8.2 -8.3 -8.27 1053 Pyrinoline ZINC000000538243 -8.3 -8.2 -8.3 -8.27 1054 Nicafenine ZINC000001846209 -8.3 -8.3 -8.2 -8.27 1055 Flotrenizine ZINC000022463051 -8.3 -8.3 -8.2 -8.27 1056 Trenizine ZINC000072266906 -8.3 -8.3 -8.2 -8.27 1057 Teopranitol ZINC000004217526 -8.3 -8.3 -8.2 -8.27 1058 Tacrolimus ZINC000085537027 -8.3 -8.3 -8.2 -8.27 1059 Palinavir ZINC000003936474 -8.3 -8.3 -8.2 -8.27 1060 Alinastine ZINC000003800366 -8.3 -8.3 -8.2 -8.27 1061 Pf-04691502 ZINC000100015733 -8.3 -8.3 -8.2 -8.27 1062 Flavodic_acid ZINC000004073414 -8.3 -8.3 -8.2 -8.27 1063 Garenoxacin ZINC000003585048 -8.3 -8.3 -8.2 -8.27 1064 Ulifloxacin ZINC000003791737 -8.3 -8.3 -8.2 -8.27 1065 Ticagrelor ZINC000143240396 -8.3 -8.4 -8.1 -8.27 1066 Carmoxirole ZINC000001533114 -8.3 -8.4 -8.1 -8.27 1067 Triacetyldiphenolisatin ZINC000004217281 -8.1 -8.1 -8.6 -8.27 1068 Lobuprofen ZINC000005138307 -8.4 -8.2 -8.2 -8.27 1069 Roxindole ZINC000001548439 -8.1 -8.3 -8.3 -8.23 1070 Raloxifene ZINC000000538275 -8.1 -8.3 -8.3 -8.23 1071 Siponimod ZINC000006717453 -8.1 -8.4 -8.2 -8.23 1072 Xenazoic-acid ZINC000000608131 -8.2 -8.2 -8.3 -8.23 1073 Moxicoumone ZINC000031291708 -8.2 -8.2 -8.3 -8.23 1074 Polydatin ZINC000106385665 -8.3 -8.1 -8.3 -8.23 1075 Ticagrelor ZINC000143240622 -8.2 -8.2 -8.3 -8.23 1076 Etibendazole ZINC000005386462 -8.2 -8.2 -8.3 -8.23 1077 Polydatin ZINC000003881962 -8.2 -8.2 -8.3 -8.23 1078 Azilsartan ZINC000000598390 -8.3 -8.2 -8.2 -8.23 1079 Proroxan ZINC000000340372 -8.2 -8.3 -8.2 -8.23 1080 Lidanserin ZINC000003775733 -8.3 -8.2 -8.2 -8.23 1081 Saviprazole ZINC000001552562 -8.2 -8.3 -8.2 -8.23 1082 ipragliflozin ZINC000138361877 -8.2 -8.3 -8.2 -8.23 1083 Revospirone ZINC000056134943 -8.2 -8.3 -8.2 -8.23 1084 Polydatin ZINC000039205864 -8.3 -8.2 -8.2 -8.23 1085 Tacrolimus ZINC000169289411 -8.3 -8.2 -8.2 -8.23 1086 Elobixibat ZINC000003976764 -8.2 -8.3 -8.2 -8.23 1087 Teniposide ZINC000150652469 -8.3 -8.2 -8.2 -8.23 1088 Mindodilol ZINC000001846111 -8.2 -8.3 -8.2 -8.23 1089 Levomefolic-acid ZINC000004228266 -8.2 -8.3 -8.2 -8.23 1090 Sb-742457 ZINC000043199965 -8.3 -8.2 -8.2 -8.23 1091 Ticagrelor ZINC000605696438 -8.2 -8.3 -8.2 -8.23 1092 Mk-0249 ZINC000038269036 -8.3 -8.2 -8.2 -8.23 1093 Etoposide ZINC000015449127 -8.2 -8.3 -8.2 -8.23 1094 Flestolol ZINC000002017625 -8.4 -8.1 -8.2 -8.23 1095 beta_Ergocryptine ZINC000100071821 -8.2 -8.3 -8.2 -8.23 1096 Pinafide ZINC000004217305 -8.2 -8.3 -8.2 -8.23 1097 Milfasartan ZINC000001539347 -8.3 -8.2 -8.2 -8.23 1098 Teniposide ZINC000150652472 -8.3 -8.2 -8.2 -8.23 1099 Declenperone ZINC000004215520 -8.3 -8.2 -8.2 -8.23 1100 Verucerfont ZINC000034661169 -8.2 -8.3 -8.2 -8.23 1101 Aseripide ZINC000082125620 -8.3 -8.2 -8.2 -8.23 1102 Reglitazar ZINC000084462508 -8.3 -8.3 -8.1 -8.23 1103 Ji-101 ZINC000038255464 -8.3 -8.3 -8.1 -8.23 1104 Eribaxaban ZINC000003816482 -8.1 -8.4 -8.1 -8.20 1105 Carmoterol ZINC000034853956 -8.2 -8.1 -8.3 -8.20 1106 Batelapine ZINC000031284355 -8.2 -8.2 -8.2 -8.20 1107 Indapamide ZINC000000643114 -8.2 -8.2 -8.2 -8.20 1108 Hydroxyestrone_diacetate ZINC000254855482 -8.2 -8.2 -8.2 -8.20 1109 Leteprinim ZINC000005117168 -8.2 -8.2 -8.2 -8.20 1110 Cianidanol ZINC000000119978 -8.2 -8.2 -8.2 -8.20 1111 Zaldaride ZINC000013813280 -8.2 -8.2 -8.2 -8.20 1112 Paraflutizide ZINC000001843075 -8.2 -8.2 -8.2 -8.20 1113 Rg-7603 ZINC000117249555 -8.2 -8.2 -8.2 -8.20 1114 Piritrexim ZINC000000000640 -8.2 -8.2 -8.2 -8.20 1115 Polydatin ZINC000012888720 -8.2 -8.2 -8.2 -8.20 1116 Sipatrigine ZINC000000538354 -8.2 -8.2 -8.2 -8.20 1117 Paranyline ZINC000001482136 -8.2 -8.2 -8.2 -8.20 1118 Doretinel ZINC000003785287 -8.2 -8.2 -8.2 -8.20 1119 Ofloxacin ZINC000000537891 -8.2 -8.2 -8.2 -8.20 1120 Clothiapine ZINC000026185346 -8.2 -8.2 -8.2 -8.20 1121 Etoposide ZINC000100042696 -8.2 -8.2 -8.2 -8.20 1122 Serazapine ZINC000000596677 -8.2 -8.2 -8.2 -8.20 1123 Bms-582949 ZINC000036475284 -8.2 -8.2 -8.2 -8.20 1124 Tak-901 ZINC000035310420 -8.2 -8.2 -8.2 -8.20 1125 Lobeglitazone ZINC000033972992 -8.2 -8.2 -8.2 -8.20 1126 Ibipinabant ZINC000003964747 -8.2 -8.2 -8.2 -8.20 1127 Tubulozole ZINC000003873396 -8.2 -8.2 -8.2 -8.20 1128 Trabodenoson ZINC000035931662 -8.2 -8.2 -8.2 -8.20 1129 Clopenthixol ZINC000000601293 -8.2 -8.2 -8.2 -8.20 1130 Enmd-2076 ZINC000060326209 -8.2 -8.2 -8.2 -8.20 1131 Azd-7762 ZINC000033359230 -8.2 -8.2 -8.2 -8.20 1132 Etoposide ZINC000003978073 -8.2 -8.2 -8.2 -8.20 1133 Bepafant ZINC000013531919 -8.2 -8.2 -8.2 -8.20 1134 Proscillaridin ZINC000257355133 -8.2 -8.2 -8.2 -8.20 1135 Cyclocumarol ZINC000004212731 -8.2 -8.2 -8.2 -8.20 1136 Hesperetin ZINC000000039091 -8.2 -8.2 -8.2 -8.20 1137 Cilansetron ZINC000000004035 -8.2 -8.2 -8.2 -8.20 1138 Sb-705498 ZINC000034297799 -8.2 -8.2 -8.2 -8.20 1139 Selprazine ZINC000033872449 -8.2 -8.2 -8.2 -8.20 1140 Polydatin ZINC000000899166 -8.2 -8.2 -8.2 -8.20 1141 Metioxate ZINC000000537994 -8.2 -8.2 -8.2 -8.20 1142 Etoposide ZINC000103553199 -8.2 -8.2 -8.2 -8.20 1143 Azelastine ZINC000000601229 -8.2 -8.2 -8.2 -8.20 1144 Solabegron ZINC000001547346 -8.3 -8.1 -8.2 -8.20 1145 Pki-166 ZINC000034032906 -8.2 -8.2 -8.2 -8.20 1146 Pholcodine ZINC000033839044 -8.2 -8.2 -8.2 -8.20 1147 Pf-00446687 ZINC000101338048 -8.2 -8.2 -8.2 -8.20 1148 Carabersat ZINC000003823825 -8.2 -8.2 -8.2 -8.20 1149 Nesbuvir ZINC000030691787 -8.2 -8.2 -8.2 -8.20 1150 Rimonabant ZINC000001540228 -8.2 -8.2 -8.2 -8.20 1151 Sparfloxacin ZINC000000538362 -8.2 -8.2 -8.2 -8.20 1152 Alatrofloxacin ZINC000100067477 -8.2 -8.2 -8.2 -8.20 1153 Reminertant ZINC000001482927 -8.2 -8.2 -8.2 -8.20 1154 Ataluren ZINC000013831791 -8.2 -8.2 -8.2 -8.20 1155 Ruzadolane ZINC000067839144 -8.2 -8.2 -8.2 -8.20 1156 Elagolix ZINC000049888891 -8.2 -8.2 -8.2 -8.20 1157 Efaproxiral ZINC000001481819 -8.2 -8.2 -8.2 -8.20 1158 Sulofenur ZINC000000538395 -8.2 -8.2 -8.2 -8.20 1159 Alvocidib ZINC000021288966 -8.2 -8.2 -8.2 -8.20 1160 Trimazosin ZINC000000601252 -8.2 -8.2 -8.2 -8.20 1161 Adomeglivant ZINC000117040417 -8.2 -8.2 -8.2 -8.20 1162 Ibipinabant ZINC000013559250 -8.2 -8.2 -8.2 -8.20 1163 Calcipotriene ZINC000038599402 -8.2 -8.2 -8.2 -8.20 1164 Bitolterol ZINC000000896452 -8.2 -8.2 -8.2 -8.20 1165 Flupentixol ZINC000028643021 -8.2 -8.2 -8.2 -8.20 1166 Galantamine ZINC000000491073 -8.2 -8.2 -8.2 -8.20 1167 Sildenafil ZINC000019796168 -8.2 -8.2 -8.2 -8.20 1168 Nimetazepam ZINC000003831205 -8.2 -8.2 -8.2 -8.20 1169 Bitopertin ZINC000053294263 -8.2 -8.2 -8.2 -8.20 1170 Reglitazar ZINC000006069082 -8.2 -8.2 -8.2 -8.20 1171 Bms-754807 ZINC000043203317 -8.2 -8.2 -8.2 -8.20 1172 Amibegron ZINC000003797401 -8.2 -8.2 -8.2 -8.20 1173 Phthalylsulfamethizole ZINC000033852268 -8.2 -8.2 -8.2 -8.20 1174 Polydatin ZINC000101954257 -8.2 -8.2 -8.2 -8.20 1175 Litomeglovir ZINC000084759446 -8.2 -8.2 -8.2 -8.20 1176 Lometrexol ZINC000008577213 -8.2 -8.2 -8.2 -8.20 1177 Mk-0533 ZINC000049878561 -8.2 -8.2 -8.2 -8.20 1178 Sulfasalazine ZINC000003831490 -8.2 -8.2 -8.2 -8.20 1179 Tonabersat ZINC000003823813 -8.2 -8.2 -8.2 -8.20 1180 Sulfasalazine ZINC000100031653 -8.2 -8.2 -8.2 -8.20 1181 Mk-7246 ZINC000034804182 -8.2 -8.2 -8.2 -8.20 1182 Yohimbic-acid ZINC000003881708 -8.2 -8.2 -8.2 -8.20 1183 Palomid-529 ZINC000043195311 -8.2 -8.2 -8.2 -8.20 1184 Crisnatol ZINC000000005042 -8.2 -8.2 -8.2 -8.20 1185 Trelnarizine ZINC000033954104 -8.2 -8.2 -8.2 -8.20 1186 Verosudil ZINC000115224602 -8.2 -8.2 -8.2 -8.20 1187 Sumarotene ZINC000001541060 -8.2 -8.2 -8.2 -8.20 1188 Piroheptine ZINC000002020004 -8.2 -8.2 -8.2 -8.20 1189 Yohimbic-acid ZINC000072186823 -8.2 -8.2 -8.2 -8.20 1190 Metrifudil ZINC000004216929 -8.2 -8.2 -8.2 -8.20 1191 Etoposide-phosphate ZINC000306146643 -8.2 -8.2 -8.2 -8.20 1192 Teniposide ZINC000095628282 -8.2 -8.2 -8.2 -8.20 1193 Teniposide ZINC000028226562 -8.2 -8.2 -8.2 -8.20 1194 Falnidamol ZINC000001494443 -8.2 -8.2 -8.2 -8.20 1195 Laquinimod ZINC000100004621 -8.2 -8.2 -8.2 -8.20 1196 Englitazone ZINC000005933617 -8.2 -8.2 -8.2 -8.20 1197 Traxoprodil ZINC000000005936 -8.2 -8.2 -8.2 -8.20 1198 Polydatin ZINC000096032072 -8.2 -8.2 -8.2 -8.20 1199 Desloratadine ZINC000000001261 -8.2 -8.2 -8.2 -8.20 1200 Trifarotene ZINC000113700519 -8.3 -8.2 -8.1 -8.20 1201 Ticagrelor ZINC000204935758 -8.2 -8.3 -8.1 -8.20 1202 Kx2-391 ZINC000043152787 -8.3 -8.2 -8.1 -8.20 1203 Raltitrexed ZINC000001625751 -8.3 -8.2 -8.1 -8.20 1204 Homopipramol ZINC000022463208 -8.2 -8.3 -8.1 -8.20 1205 Pipoxolan ZINC000002017397 -8.1 -8.1 -8.3 -8.17 1206 Velpatasvir ZINC000203686879 -8.1 -8.1 -8.3 -8.17 1207 Vipadenant ZINC000040863182 -8.2 -8.1 -8.2 -8.17 1208 Presatovir ZINC000147519584 -8.1 -8.2 -8.2 -8.17 1209 Gantofiban ZINC000022447381 -8.1 -8.2 -8.2 -8.17 1210 Nirogacestat ZINC000038217836 -8.2 -8.1 -8.2 -8.17 1211 Nelotanserin ZINC000038239930 -8.1 -8.2 -8.2 -8.17 1212 Polydatin ZINC000238785594 -8.1 -8.2 -8.2 -8.17 1213 Methotrexate ZINC000001529323 -8.2 -8.1 -8.2 -8.17 1214 Mefeserpine ZINC000004213752 -8.2 -8.1 -8.2 -8.17 1215 Luxabendazole ZINC000001842766 -8.2 -8.1 -8.2 -8.17 1216 Picotamide ZINC000000538174 -8.1 -8.2 -8.2 -8.17 1217 Pemedolac ZINC000000000590 -8.1 -8.2 -8.2 -8.17 1218 Funapide ZINC000113473392 -8.2 -8.1 -8.2 -8.17 1219 Teniposide ZINC000150652465 -8.1 -8.2 -8.2 -8.17 1220 Avanafil ZINC000011677857 -8.2 -8.1 -8.2 -8.17 1221 Palomid-529 ZINC000043195312 -8.1 -8.2 -8.2 -8.17 1222 Theodrenaline ZINC000001566349 -8.2 -8.1 -8.2 -8.17 1223 Avitriptan ZINC000000600434 -8.2 -8.1 -8.2 -8.17 1224 Teniposide ZINC000253928518 -8.1 -8.2 -8.2 -8.17 1225 Binospirone ZINC000001536786 -8.2 -8.1 -8.2 -8.17 1226 Teniposide ZINC000049605896 -8.1 -8.2 -8.2 -8.17 1227 Saviprazole ZINC000011687804 -8.2 -8.1 -8.2 -8.17 1228 Fradafiban ZINC000003789797 -8.1 -8.2 -8.2 -8.17 1229 Picoprazole ZINC000011726796 -8.1 -8.2 -8.2 -8.17 1230 Azd-7762 ZINC000034885165 -8.2 -8.2 -8.1 -8.17 1231 Panadiplon ZINC000000004220 -8.2 -8.2 -8.1 -8.17 1232 Mioflazine ZINC000022851772 -8.2 -8.2 -8.1 -8.17 1233 Siramesine ZINC000001533883 -8.2 -8.2 -8.1 -8.17 1234 Deracoxib ZINC000000607803 -8.2 -8.2 -8.1 -8.17 1235 Deserpidine ZINC000257400371 -8.2 -8.2 -8.1 -8.17 1236 Ticagrelor ZINC000143240186 -8.2 -8.2 -8.1 -8.17 1237 Edotecarin ZINC000003946372 -8.3 -8.1 -8.1 -8.17 1238 Perafensine ZINC000033852266 -8.2 -8.2 -8.1 -8.17 1239 Pipratecol ZINC000031298027 -8.2 -8.2 -8.1 -8.17 1240 Ilomastat ZINC000003872718 -8.1 -8.1 -8.2 -8.13 1241 Mofarotene ZINC000027558006 -8.1 -8.1 -8.2 -8.13 1242 Medroxalol ZINC000001570645 -8.2 -8 -8.2 -8.13 1243 Acetergamine ZINC000004172319 -8.1 -8.1 -8.2 -8.13 1244 Alpertine ZINC000004214776 -8.1 -8.1 -8.2 -8.13 1245 Polydatin ZINC000004098633 -8.1 -8.1 -8.2 -8.13 1246 Tobuterol ZINC000004214489 -8.1 -8.1 -8.2 -8.13 1247 Etoposide ZINC000003978072 -8.1 -8.1 -8.2 -8.13 1248 Arhalofenate ZINC000002012860 -8.2 -8.1 -8.1 -8.13 1249 Homofenazine ZINC000019366089 -8.2 -8.1 -8.1 -8.13 1250 Polydatin ZINC000096032073 -8.1 -8.2 -8.1 -8.13 1251 Raxatrigine ZINC000034892269 -8.2 -8.1 -8.1 -8.13 1252 Benzotript ZINC000002539823 -8.2 -8.1 -8.1 -8.13 1253 Ribociclib ZINC000072316335 -8.1 -8.2 -8.1 -8.13 1254 Terutroban ZINC000003811419 -8.1 -8.2 -8.1 -8.13 1255 Bermoprofen ZINC000001846075 -8.1 -8.2 -8.1 -8.13 1256 Levomefolic-acid ZINC000004228267 -8.2 -8.1 -8.1 -8.13 1257 Suclofenide ZINC000001842729 -8.2 -8.1 -8.1 -8.13 1258 Bexagliflozin ZINC000072319782 -8.2 -8.1 -8.1 -8.13 1259 Lefradafiban ZINC000027093989 -8.2 -8.1 -8.1 -8.13 1260 Relenopride ZINC000118666544 -8.2 -8.1 -8.1 -8.13 1261 Delavirdine ZINC000018516586 -8.2 -8.1 -8.1 -8.13 1262 Oxaflumazine ZINC000022463271 -8.2 -8.1 -8.1 -8.13 1263 Incb-9471 ZINC000043171152 -8.2 -8.1 -8.1 -8.13 1264 Oxarbazole ZINC000000000574 -8.2 -8.1 -8.1 -8.13 1265 Droperidol ZINC000019796080 -8.2 -8.1 -8.1 -8.13 1266 Pholcodine ZINC000059867903 -8.1 -8.2 -8.1 -8.13 1267 Dacuronium ZINC000004212779 -8.2 -8.1 -8.1 -8.13 1268 Trazolopride ZINC000033940852 -8.1 -8.1 -8.1 -8.10 1269 Teniposide ZINC000204007294 -8.1 -8.1 -8.1 -8.10 1270 Clidinium ZINC000000601316 -8.1 -8.1 -8.1 -8.10 1271 Pirenzepine ZINC000019632927 -8.1 -8.1 -8.1 -8.10 1272 Rispenzepine ZINC000003795847 -8.1 -8.1 -8.1 -8.10 1273 S-adenosyl-methionine ZINC000004214738 -8.1 -8.1 -8.1 -8.10 1274 Elliptinium ZINC000000001345 -8.1 -8.1 -8.1 -8.10 1275 Itraconazole ZINC000028007119 -8.1 -8.1 -8.1 -8.10 1276 Ipsalazide ZINC000004216628 -8.1 -8.1 -8.1 -8.10 1277 Pipamazine ZINC000000538183 -8.1 -8.1 -8.1 -8.10 1278 Bunazosin ZINC000000601249 -8.1 -8.1 -8.1 -8.10 1279 Acoxatrine ZINC000001640527 -8.1 -8.1 -8.1 -8.10 1280 Pf-04691502 ZINC000117704832 -8.1 -8.1 -8.1 -8.10 1281 Indiplon ZINC000000538650 -8.1 -8.1 -8.1 -8.10 1282 Ticagrelor ZINC000306122927 -8.1 -8.1 -8.1 -8.10 1283 Prasterone_acetate ZINC000253608411 -8.1 -8.1 -8.1 -8.10 1284 Betrixaban ZINC000030691754 -8.1 -8.1 -8.1 -8.10 1285 Pipecuronium ZINC000003938681 -8.1 -8.1 -8.1 -8.10 1286 Olmesartan ZINC000000538621 -8.1 -8.1 -8.1 -8.10 1287 Pipramadol ZINC000004214155 -8.1 -8.1 -8.1 -8.10 1288 Polydatin ZINC000005923206 -8.1 -8.1 -8.1 -8.10 1289 Sivifene ZINC000003914981 -8.1 -8.1 -8.1 -8.10 1290 Mebendazole ZINC000000121541 -8.1 -8.1 -8.1 -8.10 1291 Pimethixene ZINC000000000627 -8.1 -8.1 -8.1 -8.10 1292 Axitinib ZINC000003816287 -8.1 -8.1 -8.1 -8.10 1293 Trifezolac ZINC000000538502 -8.1 -8.1 -8.1 -8.10 1294 Trazodone ZINC000000538483 -8.1 -8.1 -8.1 -8.10 1295 Orteronel ZINC000003943521 -8.1 -8.1 -8.1 -8.10 1296 Onalespib ZINC000043208226 -8.1 -8.1 -8.1 -8.10 1297 Leucocianidol ZINC000003591028 -8.1 -8.1 -8.1 -8.10 1298 Suronacrine ZINC000000004267 -8.1 -8.1 -8.1 -8.10 1299 Palonosetron ZINC000003795819 -8.1 -8.1 -8.1 -8.10 1300 Amp579 ZINC000256226379 -8.1 -8.1 -8.1 -8.10 1301 Bisfenazone ZINC000000608210 -8.1 -8.1 -8.1 -8.10 1302 Praziquantel ZINC000000000655 -8.1 -8.1 -8.1 -8.10 1303 Ly-518674 ZINC000000595076 -8.1 -8.1 -8.1 -8.10 1304 Tipentosin ZINC000002014159 -8.1 -8.1 -8.1 -8.10 1305 At-7519 ZINC000016052857 -8.1 -8.1 -8.1 -8.10 1306 Cep-5214 ZINC000001551940 -8.1 -8.1 -8.1 -8.10 1307 Yohimbic-acid ZINC000003947438 -8.1 -8.1 -8.1 -8.10 1308 Flupranone ZINC000000537749 -8.1 -8.1 -8.1 -8.10 1309 Adibendan ZINC000000000883 -8.1 -8.1 -8.1 -8.10 1310 Alnespirone ZINC000003635820 -8.1 -8.1 -8.1 -8.10 1311 Taglutimide ZINC000017161200 -8.1 -8.1 -8.1 -8.10 1312 Pf-04691502 ZINC000058660483 -8.1 -8.1 -8.1 -8.10 1313 Diphenadione ZINC000100044649 -8.1 -8.1 -8.1 -8.10 1314 Tolnidamine ZINC000000002192 -8.1 -8.1 -8.1 -8.10 1315 Lonidamine ZINC000000001632 -8.1 -8.1 -8.1 -8.10 1316 Protokylol ZINC000001704228 -8.1 -8.1 -8.1 -8.10 1317 Zometapine ZINC000000002263 -8.1 -8.1 -8.1 -8.10 1318 Bevonium ZINC000000607738 -8.1 -8.1 -8.1 -8.10 1319 Erteberel ZINC000012353762 -8.1 -8.1 -8.1 -8.10 1320 Fluindarol ZINC000100229169 -8.1 -8.1 -8.1 -8.10 1321 Suclofenide ZINC000100368602 -8.1 -8.1 -8.1 -8.10 1322 S-adenosyl-methionine ZINC000012371977 -8.1 -8.1 -8.1 -8.10 1323 Bifonazole ZINC000003812958 -8.1 -8.1 -8.1 -8.10 1324 Dalvastatin ZINC000000597504 -8.1 -8.1 -8.1 -8.10 1325 Trazium ZINC000005935149 -8.1 -8.1 -8.1 -8.10 1326 Etoposide ZINC000003830819 -8.1 -8.1 -8.1 -8.10 1327 Benzylhydrochlorothiazide ZINC000000607731 -8.1 -8.1 -8.1 -8.10 1328 Ticagrelor ZINC000095626794 -8.1 -8.1 -8.1 -8.10 1329 Trefentanil ZINC000000538484 -8.1 -8.1 -8.1 -8.10 1330 Flunarizine ZINC000019360739 -8.1 -8.1 -8.1 -8.10 1331 Xinidamine ZINC000000002246 -8.1 -8.1 -8.1 -8.10 1332 Butaclamol ZINC000002008410 -8.1 -8.1 -8.1 -8.10 1333 Tolpadol ZINC000031297954 -8.1 -8.1 -8.1 -8.10 1334 Polydatin ZINC000065748638 -8.1 -8.1 -8.1 -8.10 1335 Indoramin ZINC000000001567 -8.1 -8.1 -8.1 -8.10 1336 Englitazone ZINC000005933666 -8.1 -8.1 -8.1 -8.10 1337 Propisergide ZINC000059868006 -8.1 -8.1 -8.1 -8.10 1338 Upadacitinib ZINC000147180128 -8.1 -8.1 -8.1 -8.10 1339 Bretazenil ZINC000000597316 -8.1 -8.1 -8.1 -8.10 1340 Orotirelin ZINC000004217208 -8.1 -8.1 -8.1 -8.10 1341 Calcipotriene ZINC000038791645 -8.1 -8.1 -8.1 -8.10 1342 Etisulergine ZINC000004215916 -8.1 -8.1 -8.1 -8.10 1343 Pirinixil ZINC000001846197 -8.1 -8.1 -8.1 -8.10 1344 Hydroxyestrone_diacetate ZINC000079199213 -8.1 -8.1 -8.1 -8.10 1345 Moricizine ZINC000019340795 -8.1 -8.1 -8.1 -8.10 1346 Ly-2874455 ZINC000113514935 -8.1 -8.1 -8.1 -8.10 1347 Buclizine ZINC000019364226 -8.1 -8.1 -8.1 -8.10 1348 Benazeprilat ZINC000003814184 -8.1 -8.1 -8.1 -8.10 1349 Omidoline ZINC000005318621 -8.1 -8.1 -8.1 -8.10 1350 Alvimopan ZINC000003782341 -8.1 -8.1 -8.1 -8.10 1351 Englitazone ZINC000005933664 -8.1 -8.1 -8.1 -8.10 1352 Lonafarnib ZINC000003950115 -8.1 -8.1 -8.1 -8.10 1353 Teniposide ZINC000077313306 -8.1 -8.1 -8.1 -8.10 1354 Regadenoson ZINC000013818943 -8.1 -8.1 -8.1 -8.10 1355 Alpelisib ZINC000169302884 -8.1 -8.1 -8.1 -8.10 1356 Bromoxanide ZINC000056897575 -8.1 -8.1 -8.1 -8.10 1357 Sulindac ZINC000012503133 -8.1 -8.1 -8.1 -8.10 1358 Talnetant ZINC000001543566 -8.1 -8.1 -8.1 -8.10 1359 Buclizine ZINC000019364228 -8.1 -8.1 -8.1 -8.10 1360 Hesperetin ZINC000000039092 -8.1 -8.1 -8.1 -8.10 1361 Melitracen ZINC000001482101 -8.1 -8.1 -8.1 -8.10 1362 Axitirome ZINC000011677432 -8.1 -8.1 -8.1 -8.10 1363 Dapitant ZINC000003932681 -8.1 -8.1 -8.1 -8.10 1364 Ac-430 ZINC000095079936 -8.1 -8.1 -8.1 -8.10 1365 Nifurfoline ZINC000038609700 -8.1 -8.1 -8.1 -8.10 1366 Bms-863233 ZINC000299853377 -8.1 -8.1 -8.1 -8.10 1367 Adosopine ZINC000000012519 -8.1 -8.1 -8.1 -8.10 1368 Sitogluside ZINC000085532584 -8.1 -8.1 -8.1 -8.10 1369 Rubitecan ZINC000003827362 -8.1 -8.1 -8.1 -8.10 1370 Vismodegib ZINC000040899447 -8.1 -8.1 -8.1 -8.10 1371 Neldazosin ZINC000000607988 -8.1 -8.1 -8.1 -8.10 1372 Doretinel ZINC000011679570 -8.1 -8.1 -8.1 -8.10 1373 Tolvaptan ZINC000001490477 -8.1 -8.1 -8.1 -8.10 1374 Leucocianidol ZINC000004213653 -8.1 -8.1 -8.1 -8.10 1375 S-adenosyl-methionine ZINC000095644663 -8.1 -8.1 -8.1 -8.10 1376 S-adenosyl-methionine ZINC000071755565 -8.1 -8.1 -8.1 -8.10 1377 Selodenoson ZINC000003989599 -8.1 -8.1 -8.1 -8.10 1378 Proroxan ZINC000003087481 -8.1 -8 -8.1 -8.07 1379 Rafabegron ZINC000003952725 -8.1 -8.1 -8 -8.07 1380 Vandetanib ZINC000053683345 -8 -8.1 -8.1 -8.07 NSP16- total Sup Fig and tab (5-6-2020).pdf (2.42 MiB) view on ChemRxiv download file