China Japan United States Europe

Total Page:16

File Type:pdf, Size:1020Kb

China Japan United States Europe Inhibitor United States China Toll Free: +1 877 796-6397 Toll Free: 400-668-6834 Fax: +1 832 582-8590 Fax: 021-68591981 E-mail: [email protected] E-mail: [email protected] Europe Japan Tel: +49-89-46148500 Tel: + 81 3-5632-9610 Fax: +49-89-461485022 Fax: + 81 3-5632-9619 E-mail: [email protected] E-mail: [email protected] Protein Tyrosine Kinase PI3K/Akt/mTOR MAPK Inhibitors Cytoskeletal Signaling Selleck Chemicals supplies over 3,000 Apoptosis + inhibitors used in the study of cell 3000 Epigenetics Cell Cycle Inhibitors signaling pathways. Ubiquitin Signaling DNA Damage Stem Others Cells Neuronal Signaling Product Citations Selleck products have been cited in more than 12000 studies from various SCI journals. (Cell, Nature, Science: 61 studies) Compound Libraries Bioactive Compound Library 2659 compounds Nature. 2017, 541(7638):481-487. Nature. 2015, 521(7552):357-61. Science. 2016, 354(6315). Nature. 2017, 10.1038/nature21064. Nature. 2015, 521(7552):316-21. Science. 2016, 353(6302):929-32. Kinase Inhibitor Library Nature. 2016, 540(7631):119-123. Nature. 2015, 520(7549):683-7. Science. 2016, 352(6283):353-8. 430 inhibitors Nature. 2016, 539(7629):437-442. Nature. 2015, 520(7547):368-72. Science. 2016, 352(6282):189-96. Nature. 2016, 539(7628):304-308. Nature. 2015, 519(7543):370-3. Science. 2016, 351(6277):aad3680. FDA-approved Drug Library 1443 compounds Nature. 2016, 539(7627):54-58. Nature. 2015, 518(7538):254-7. Science. 2013, 341(6146):651-4. Nature. 2016, 538(7626):477-482. Nature. 2015, 517(7536):583-8. Science. 2013, 339(6120):700-4. Inhibitor Library Nature. 2016, 537(7620):422-426. Nature. 2015, 517(7535):460-5. Cell. 2017, 168(5):856-866. 1695 inhibitors Nature. 2016, 535(7613):517-22. Nature. 2015, 517(7534):391-5. Cell. 2017, 168(1-2):86-100. Epigenetics Compound Library Tyrosine Kinase Inhibitor Library Nature. 2016, 534(7607):341-6. Nature. 2014, 511(7507):90-3. Cell. 2016, 167(7):1803-1813. 182 small molecule modulators 171 tyrosine kinase inhibitors Nature. 2016, 532(7597):107-11. Nature. 2014, 510(7504):283-7. Cell. 2016, 167(1):233-247. Nature. 2016, 531(7596):651-5. Nature. 2014, 509(7498):105-9. Cell. 2016, 165(1):234-46. Target Selective Inhibitor Library Stem Cell Signaling Compound Library Nature. 2016, 530(7590):358-61. Nature. 2014, 508(7494):118-22. Cell. 2016, 164(1-2):293-309. Bioactive compounds covering over 174 targets 89 small molecule inhibitors Nature. 2015, 528(7582):422-6. Nature. 2013, 501(7466):237-41. Cell. 2015, 162(2):441-51. Natural Product Library Autophagy Compound Library Nature. 2015, 527(7576):100-4. Nature. 2013, 500(7461):222-6. Cell. 2015, 160(1-2):161-76. 133 natural products 154 autophagy signaling pathway ihibitors Nature. 2015, 524(7566):471-5. Nature. 2013, 498(7452):109-12. Cell. 2014, 159(5):1110-25. Nature. 2015, 523(7558):92-5. Nature. 2013, 496(7446):523-7. Cell. 2014, 158(5):989-99. GPCR Compound Library Ion Channel Ligand Library Nature. 2015, 522(7557):492-6. Nature. 2013, 493(7430):51-5. Cell. 2013, 154(5):1036-46. 280 GPCR small molecule compounds 63 ion channel ligands Nature. 2015, 522(7556):349-53. Science. 2017, eaal3755. Cell. 2013, 153(4):840-54. Anti-cancer Compound Library ... Nature. 2015, 522(7555):226-30. Science. 2017, 355(6320):84-88. 422 anti-cancer compounds Nature. 2015, 521(7553):541-4. Science. 2017, 355(6320):78-83. Customize your library by selecting compounds of interest. Selleck is a Licensed Supplier of Pfizer Compounds Table of Contents Compound Libraries Bioactive Compound Library 1 FDA-approved Drug Library 2 Other Compound Libraries 3 Inhibitors PI3K/Akt/mTOR Pathway PI3K 5 mTOR 10 In 2013, Selleck became a licensed supplier of Pfizer pharmaceuticals. This has granted our Akt 12 customers access to Pfizer’s exclusive and high quality compounds. Purchased individually or GSK-3 13 as a library, these compounds have a wide range of applications in preclinical research of ATM/ATR 14 human diseases. PDK-1 15 S6 Kinase 16 ◆ All bioactive compounds are licensed by Pfizer and have been marketed and/or have been clinically AMPK 16 demonstrated to be safe and efficacious in humans. DNA-PK 17 MELK 17 ◆ Compounds span a range of potential uses: from anti-cancer compounds (e.g. Bosutinib) to a glycylcycline antiobiotic (e.g. Tigecycline) to combat the growing prevalence of antibiotic resistance. ◆ Reliability Guarantee: all Pfizer licensed compounds are developed and validated by Pfizer - some of Epigenetics HDAC 18 which are manufactured by Pfizer Quality Assurance: all compounds are validated using NMR and HPLC. PARP 22 JAK 23 ◆ Detailed preclinical research data and safety information available. Pim 25 HIF 25 Aurora Kinase 26 Sirtuin 28 Epigenetic Reader Domain 29 Histone Acetyltransferase 30 DNA Methyltransferase 30 Histone Methyltransferase 31 Histone Demethylase 32 Protein Tyrosine Kinase VEGFR 33 EGFR 36 PDGFR 39 Protein Tyrosine Kinase c-Met 40 Autophagy Autophagy 58 HER2 41 LRRK2 59 IGF-1R 42 FLT3 43 JAK/STAT Pathway JAK 60 FGFR 44 STAT 60 c-Kit 45 EGFR 60 ALK 45 Pim 60 Tie-2 46 c-RET 46 Trk Receptor 46 MAPK MEK 62 Ephrin Receptor 46 Raf 64 CSF-1R 47 p38 MAPK 65 TAM Receptor 47 JNK 66 ERK 67 Angiogenesis VEGFR 48 JAK 48 Cytoskeletal Signaling Akt 68 EGFR 48 Wnt/beta-catenin 68 PDGFR 48 Bcr-Abl 68 HER2 48 FAK 68 FLT3 48 PKC 69 FGFR 48 HSP (e.g. HSP90) 70 ALK 48 Kinesin 72 HIF 48 Microtubule Associated 73 VDA 49 Integrin 74 Bcr-Abl 49 PAK 74 Src 50 Dynamin 74 Syk 51 FAK 52 Cell Cycle CDK 75 BTK 52 Aurora Kinase 75 Chk 78 Apoptosis c-RET 53 ROCK 79 Bcl-2 53 PLK 80 Caspase 54 APC 80 p53 55 Wee1 80 TNF-alpha 55 Rho 80 Mdm2 56 c-Myc 81 Survivin 56 PD-1/PD-L1 81 IAP 57 PERK 57 TGF-beta/Smad Pathway TGF-beta/Smad 82 Neuronal Signaling Histamine Receptor 97 Bcr-Abl 82 Dopamine Receptor 97 ROCK 82 Opioid Receptor 98 PKC 82 GABA Receptor 98 P-gp 98 P2 Receptor 99 DNA Damage HDAC 84 OX Receptor 99 ATM/ATR 84 MT Receptor 99 PARP 84 BACE 99 DNA/RNA Synthesis 84 CaMK 99 Sirtuin 84 DNA-PK 84 Topoisomerase 86 NF-κB Pathway HDAC 100 Telomerase 87 NF-κB 100 IκB/IKK 101 NOD1 101 Stem Cells & Wnt Pathway GSK-3 88 JAK 88 STAT 88 GPCR & G Protein 5-HT Receptor 102 TGF-beta/Smad 88 Adrenergic Receptor 102 Wnt/beta-catenin 88 Histamine Receptor 102 ROCK 88 OX Receptor 102 Gamma-secretase 88 Dopamine Receptor 102 Hedgehog/Smoothened 89 Opioid Receptor 102 Casein Kinase 90 Hedgehog/Smoothened 102 MT Receptor 102 Ubiquitin Pathway Proteasome 91 Cannabinoid Receptor 103 DUB 92 Endothelin Receptor 103 p97 93 S1P Receptor 103 E2 Conjugating 93 SGLT 103 E1 Activating 93 LPA Receptor 103 E3 Ligase 93 CGRP Receptor 104 PAFR 104 CaSR 104 Neuronal Signaling Gamma-secretase 94 Vasopressin Receptor 104 Beta Amyloid 94 CXCR 104 5-HT Receptor 94 cAMP 104 COX 95 Adenosine Receptor 104 GluR 96 Adrenergic Receptor 96 AChR 97 Endocrinology & Hormones Opioid Receptor 105 Proteases Proteasome 119 5-alpha Reductase 105 Caspase 119 Estrogen/progestogen Receptor 105 Gamma-secretase 119 Androgen Receptor 106 HCV Protease 119 RAAS 107 DPP-4 120 Aromatase 108 HIV Protease 120 GPR 108 MMP 120 Cysteine Protease 121 Serine Protease 121 Transmembrane Transporters GABA Receptor 109 P-gp 109 Calcium Channel 109 Microbiology HCV Protease 122 Sodium Channel 110 HIV Protease 122 ATPase 110 Integrase 122 Potassium Channel 110 Reverse Transcriptase 123 Proton Pump 111 CCR 123 CFTR 111 Antifection 124 CRM1 111 TRPV 111 Metabolism HSP (e.g. HSP90) 112 Others Phosphorylase 125 PPAR 112 IL Receptor 125 P450 (e.g. CYP17) 113 Thrombin 125 PDE 113 Liver X Receptor 125 Hydroxylase 114 PKA 125 Factor Xa 114 Substance P 125 DHFR 115 FXR 125 Aminopeptidase 115 gp120/CD4 126 Dehydrogenase 115 phosphatase 126 Procollagen C Proteinase 115 NADPH oxidase 126 Carbonic Anhydrase 116 PTEN 126 MAO 116 Others 126 Phospholipase (e.g. PLA) 116 FAAH 116 IDO 116 Transferase 117 HMG-CoA Reductase 117 CETP 118 Ferroptosis 118 Vitamin 118 AhR 118 Bioactive Compound Library Cat.No. L1700 FDA-approved Drug Library Cat.No. L1300 • A unique collection of 2659 bioactive chemical compounds for high throughput screening (HTS) • A unique collection of 1443 FDA approved drugs for high throughput screening (HTS) and high and high content screening (HCS). content screening (HCS). • Bioactivity and safety confirmed by preclinical research and clinical trials. • Locate new targets for old drugs. • Some compounds have been approved by the FDA. • Bioactivity and safety confirmed by clinical trials. • Includes most Selleck inhibitors, APIs, natural products, and chemotherapeutic agents. • All compounds have been approved by FDA. • Structurally diverse, medicinally active, and cell permeable. • Related to oncology, cardiology, anti-inflammatory, immunology, neuropsychiatry, analgesia etc. • Rich documentation with structure, IC50, and customer reviews. • Structurally diverse, medicinally active, and cell permeable. • NMR and HPLC validated to ensure high purity. • Rich documentation with structure, IC50, and customer reviews. • NMR and HPLC validated to ensure high purity. Size (Pre-dissolved in DMSO) Customize Your Library You can select: Size (Pre-dissolved in DMSO) Customize Your Library 100 μL/well (10 mM solution) You can select: 100 μL/well (10 mM solution) 2x100 μL/well (10 mM solution) Specific Quantities Plate map Format (Dry/solid or Compounds DMSO solution) 2x100 μL/well (10 mM solution) Specific Quantities Plate map Format (Dry/solid or Compounds DMSO solution) Bioactive Compounds Library Composition 600 FDA-approved Compounds Library Composition 450 500 400 350 400 300 250 300 200 150 200 100 50 100 0 Other Targets 0 Other Targets Journals Citing of this Library Journals Citing of this Library Nat Prod Rep, 2014, 31(6):718-29 , 6:33427 Sci Rep, 2016 Clin Cancer Res, 2016, 10.1158/1078-0 , 16(3) Sensors (Basel), 2016 Cancer Res, 2014, 74:1702 , 6(3):1531-43 Oncotarget, 2015 Drug Discov Today, 2017, 22(2):199-203 , 20(9):1171-7 J Biomol Screen, 2015 …… …… 1 Excellent Validation, Technical Support and Prompt Delivery www.selleckchem.com 2 Other Compound Libraries Kinase Inhibitor Library Cat.No.
Recommended publications
  • Aurora Kinase a in Gastrointestinal Cancers: Time to Target Ahmed Katsha1, Abbes Belkhiri1, Laura Goff3 and Wael El-Rifai1,2,4*
    Katsha et al. Molecular Cancer (2015) 14:106 DOI 10.1186/s12943-015-0375-4 REVIEW Open Access Aurora kinase A in gastrointestinal cancers: time to target Ahmed Katsha1, Abbes Belkhiri1, Laura Goff3 and Wael El-Rifai1,2,4* Abstract Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. During the last two decades, several studies have shown amplification and overexpression of Aurora kinase A (AURKA) in several GI malignancies. These studies demonstrated that AURKA not only plays a role in regulating cell cycle and mitosis, but also regulates a number of key oncogenic signaling pathways. Although AURKA inhibitors have moved to phase III clinical trials in lymphomas, there has been slower progress in GI cancers and solid tumors. Ongoing clinical trials testing AURKA inhibitors as a single agent or in combination with conventional chemotherapies are expected to provide important clinical information for targeting AURKA in GI cancers. It is, therefore, imperative to consider investigations of molecular determinants of response and resistance to this class of inhibitors. This will improve evaluation of the efficacy of these drugs and establish biomarker based strategies for enrollment into clinical trials, which hold the future direction for personalized cancer therapy. In this review, we will discuss the available data on AURKA in GI cancers. We will also summarize the major AURKA inhibitors that have been developed and tested in pre-clinical and clinical settings. Keywords: Aurora kinases, Therapy, AURKA inhibitors, MNL8237, Alisertib, Gastrointestinal, Cancer, Signaling pathways Introduction stage [9-11]. Furthermore, AURKA is critical for Mitotic kinases are the main proteins that coordinate ac- bipolar-spindle assembly where it interacts with Ran- curate mitotic processing [1].
    [Show full text]
  • Long-Acting Cabotegravir: the Future of HIV Prep
    Long-Acting Injectable Cabotegravir: the Future of HIV PrEP? Brian R. Wood, MD Associate Professor of Medicine University of Washington Mountain West AIDS Education & Training Center June 4, 2020 Disclosures No conflicts of interest or relationships to disclose. Will be discussing an investigational antiretroviral. Full HPTN 083 study results not yet available. Will be reviewing data from a preliminary DSMB analysis today. See press release and webinar: https://www.hptn.org/news-and-events/announcements/cab- la-proves-be-highly-effective-prevention-hiv-acquisition Outline • General notes about cabotegravir • News from the phase 3 PrEP trial (and why it’s a big deal) • Questions, concerns, and next steps for long-acting PrEP What is Cabotegravir? Cabotegravir (CAB) • Investigational integrase strand transfer inhibitor • Potential infrequent dosing and parenteral administration - Oral half-life: 40 hours - Parenteral nanosuspension (IM, SC) half-life: 21-50 days - Median time from discontinuation to undetectable plasma level (IM, SC): 43-66 weeks • Metabolized by UGT1A1 (main pathway) & UGT1A9 - Minimal CYP metabolism; likely few drug interactions • Relatively low barrier to resistance Aidsinfo.nih.gov/drugs Injectable Long-Acting Cabotegravir Image courtesy of Dr. Raphael Landovitz, UCLA What is the HPTN 083 Trial and What’s the Big News? HPTN 083 A Phase 2b/3 Double Blind Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral TDF/FTC, for Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and TranHPTNsgender Women wh o 083have Sex wi thSites Men – Phase 2b/3 Target enrollment: 4,500 HIV- uninfected cisgender men and transgender 45 Sites in 8 Countrieswomen who have sex with men and who are at risk of HIV acquisition Primary outcome: HIV Prevention effectiveness of cabotegravir compared to daily oral TDF/FTC United States India Vietnam Thailand Peru Brazil South Argentina Africa ClinicalTrials.gov Identifier: NCT02720094 Slide courtesy of Dr.
    [Show full text]
  • Histone Deacetylase Inhibitors: an Attractive Therapeutic Strategy Against Breast Cancer
    ANTICANCER RESEARCH 37 : 35-46 (2017) doi:10.21873/anticanres.11286 Review Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer CHRISTOS DAMASKOS 1,2* , SERENA VALSAMI 3* , MICHAEL KONTOS 4* , ELEFTHERIOS SPARTALIS 2, THEODOROS KALAMPOKAS 5, EMMANOUIL KALAMPOKAS 6, ANTONIOS ATHANASIOU 4, DEMETRIOS MORIS 7, AFRODITE DASKALOPOULOU 2,8 , SPYRIDON DAVAKIS 4, GERASIMOS TSOUROUFLIS 1, KONSTANTINOS KONTZOGLOU 1, DESPINA PERREA 2, NIKOLAOS NIKITEAS 2 and DIMITRIOS DIMITROULIS 1 1Second Department of Propedeutic Surgery, 4First Department of Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2N.S. Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 3Blood Transfusion Department, Aretaieion Hospital, Medical School, National and Kapodistrian Athens University, Athens, Greece; 5Assisted Conception Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 6Gynaecological Oncology Department, University of Aberdeen, Aberdeen, U.K.; 7Lerner Research Institute, Cleveland Clinic, Cleveland, OH, U.S.A; 8School of Biology, National and Kapodistrian University of Athens, Athens, Greece Abstract. With a lifetime risk estimated to be one in eight in anticipate further clinical benefits of this new class of drugs, industrialized countries, breast cancer is the most frequent
    [Show full text]
  • Erteberel (LY500307) Product Data Sheet
    Product Name: Erteberel (LY500307) Revision Date: 01/10/2021 Product Data Sheet Erteberel (LY500307) Cat. No.: B1518 CAS No.: 533884-09-2 Formula: C18H18O3 M.Wt: 282.33 Synonyms: Target: Endocrinology and Hormones Pathway: Estrogen/progestogen Receptor Storage: Store at -20°C Solvent & Solubility insoluble in H2O; ≥14.1 mg/mL in DMSO; ≥48.3 mg/mL in EtOH Mass Solvent 1mg 5mg 10mg Preparing Concentration In Vitro Stock Solutions 1 mM 3.5420 mL 17.7098 mL 35.4195 mL 5 mM 0.7084 mL 3.5420 mL 7.0839 mL 10 mM 0.3542 mL 1.7710 mL 3.5420 mL Please refer to the solubility information to select the appropriate solvent. Biological Activity Shortsummary ERβ agonist, potent and selective IC₅₀ & Target Cell Viability Assay Cell Line: Human prostate cancer cell line (PC-3 cells) Preparation method: The solubility of this compound in DMSO is >10 mM. General tips for obtaining In Vitro a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. Reacting conditions: N/A 1 | www.apexbt.com Applications: Erteberel showed potent and selective binding affinity for ERβ with EC50 value of 0.66 nM [1]. Animal experiment Animal models: Male and female rat fertility and rat and rabbit embryo-fetal development model Dosage form: 0.03 to 10 mg/kg/day for rats, or 1 to 25 mg/kg/day for rabbits, oral gavage, for 2 or 10 weeks Applications: There were no-observed adverse effect levels following LY500307 In Vivo administration of 1 mg/kg/day for male rat fertility, 0.3 mg/kg/day for female rat fertility and embryo-fetal development, and 25 mg/kg/day for rabbit embryo-fetal development [2].
    [Show full text]
  • LATTE Study Oral Cabotegravir + Rilpivirine Versus Efavirenz + 2 NRTI’S LATTE Study: Design
    Oral Cabotegravir + Rilpivirine versus Efavirenz + 2 NRTI’s LATTE Study Oral Cabotegravir + Rilpivirine versus Efavirenz + 2 NRTI’s LATTE Study: Design Study Design: CAB 10 mg CAB 10 mg + 2 NRTI’s + RPV 25 mg • BacKground: Phase 2b, (n = 60) (n = 52) randoMized, partially blinded study done at Multiple centers CAB 30 mg CAB 30 mg in the U.S. and Canada + 2 NRTI’s + RPV 25 mg (n = 60) (n = 51) • Inclusion Criteria (n = 244) - Age ≥18 years - Antiretroviral-naïve CAB 60 mg CAB 60 mg - HIV RNA >1,000 copies/ML + 2 NRTI’s + RPV 25 mg - CD4 count >200 cells/MM3 (n = 61) (n = 53) - CrCl >50 ML/Min - No hepatitis B Efavirenz 600 mg Efavirenz 600 mg - No significant transaMinitis + 2 NRTI’s + 2 NRTI’s (n = 62) (n = 46) 24-week lead-in phase Source: Margolis DA, et al. Lancet Infect Dis. 2015;15:1145-55. Oral Cabotegravir + Rilpivirine versus Efavirenz + 2 NRTI’s LATTE Study: Results Cabotegravir + 2NRTIs Cabotegravir + Rilpivirine Efavirenz + 2NRTIs Induction* Maintenance* 100 80 86 82 76 74 71 60 63 40 HIV RNA <50 copies/mL (%) <50 copies/mL HIV RNA 20 156/181 46/62 149/181 44/62 137/181 39/62 0 Week 24 Week 48 Week 96 *Cabotegravir data is composite of all cabotegravir doses Source: Margolis DA, et al. Lancet Infect Dis. 2015;15:1145-55. Oral Cabotegravir + Rilpivirine versus Efavirenz + 2 NRTI’s LATTE Study: Results 100 Induction* Maintenance 80 60 Cabotegravir 10 mg + Rilpivirine 40 Cabotegravir 30 mg + Rilpivirine HIV RNA <40 copies/mL HIV RNA 20 Cabotegravir 60 mg + Rilpivirine Efavirenz 600 mg + 2NRTIs 0 0 12 24 36 48 60 72 84 96 Treatment Week *During induction phase cabotegravir administered with investigator chosen 2NRTIs Source: Margolis DA, et al.
    [Show full text]
  • An Overview of the Role of Hdacs in Cancer Immunotherapy
    International Journal of Molecular Sciences Review Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy Debarati Banik, Sara Moufarrij and Alejandro Villagra * Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, 800 22nd St NW, Suite 8880, Washington, DC 20052, USA; [email protected] (D.B.); [email protected] (S.M.) * Correspondence: [email protected]; Tel.: +(202)-994-9547 Received: 22 March 2019; Accepted: 28 April 2019; Published: 7 May 2019 Abstract: Long-standing efforts to identify the multifaceted roles of histone deacetylase inhibitors (HDACis) have positioned these agents as promising drug candidates in combatting cancer, autoimmune, neurodegenerative, and infectious diseases. The same has also encouraged the evaluation of multiple HDACi candidates in preclinical studies in cancer and other diseases as well as the FDA-approval towards clinical use for specific agents. In this review, we have discussed how the efficacy of immunotherapy can be leveraged by combining it with HDACis. We have also included a brief overview of the classification of HDACis as well as their various roles in physiological and pathophysiological scenarios to target key cellular processes promoting the initiation, establishment, and progression of cancer. Given the critical role of the tumor microenvironment (TME) towards the outcome of anticancer therapies, we have also discussed the effect of HDACis on different components of the TME. We then have gradually progressed into examples of specific pan-HDACis, class I HDACi, and selective HDACis that either have been incorporated into clinical trials or show promising preclinical effects for future consideration.
    [Show full text]
  • Structure-Based Discovery and Bioactivity Evaluation of Novel
    molecules Article Structure-Based Discovery and Bioactivity Evaluation of Novel Aurora-A Kinase Inhibitors as Anticancer Agents via Docking-Based Comparative Intermolecular Contacts Analysis (dbCICA) Majd S. Hijjawi 1 , Reem Fawaz Abutayeh 2 and Mutasem O. Taha 3,* 1 Department of Pharmacology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan; [email protected] 2 Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Science Private University, Amman 11931, Jordan; [email protected] 3 Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Amman 11942, Jordan * Correspondence: [email protected]; Tel.: +962-6-535-5000 Academic Editors: Helen Osborn, Mohammad Najlah, Jean Jacques Vanden Eynde, Annie Mayence and Tien L. Huang Received: 15 October 2020; Accepted: 11 December 2020; Published: 18 December 2020 Abstract: Aurora-A kinase plays a central role in mitosis, where aberrant activation contributes to cancer by promoting cell cycle progression, genomic instability, epithelial-mesenchymal transition, and cancer stemness. Aurora-A kinase inhibitors have shown encouraging results in clinical trials but have not gained Food and Drug Administration (FDA) approval. An innovative computational workflow named Docking-based Comparative Intermolecular Contacts Analysis (dbCICA) was applied—aiming to identify novel Aurora-A kinase inhibitors—using seventy-nine reported Aurora-A kinase inhibitors to specify the best possible docking settings needed to fit into the active-site binding pocket of Aurora-A kinase crystal structure, in a process that only potent ligands contact critical binding-site spots, distinct from those occupied by less-active ligands. Optimal dbCICA models were transformed into two corresponding pharmacophores.
    [Show full text]
  • Targeting Fibrosis in the Duchenne Muscular Dystrophy Mice Model: an Uphill Battle
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.20.427485; this version posted January 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Title: Targeting fibrosis in the Duchenne Muscular Dystrophy mice model: an uphill battle 2 Marine Theret1#, Marcela Low1#, Lucas Rempel1, Fang Fang Li1, Lin Wei Tung1, Osvaldo 3 Contreras3,4, Chih-Kai Chang1, Andrew Wu1, Hesham Soliman1,2, Fabio M.V. Rossi1 4 1School of Biomedical Engineering and the Biomedical Research Centre, Department of Medical 5 Genetics, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada 6 2Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Minia 7 University, Minia, Egypt 8 3Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, 9 Darlinghurst, NSW, 2010, Australia 10 4Departamento de Biología Celular y Molecular and Center for Aging and Regeneration (CARE- 11 ChileUC), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 12 Santiago, Chile 13 # Denotes Co-first authorship 14 15 Keywords: drug screening, fibro/adipogenic progenitors, fibrosis, repair, skeletal muscle. 16 Correspondence to: 17 Marine Theret 18 School of Biomedical Engineering and the Biomedical Research Centre 19 University of British Columbia 20 2222 Health Sciences Mall, Vancouver, British Columbia 21 Tel: +1(604) 822 0441 fax: +1(604) 822 7815 22 Email: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.20.427485; this version posted January 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]
  • Viiv Healthcare Drug Class1,4: Antiretroviral Agent, Integrase
    Brand Name: Tivicay Generic Name: dolutegravir Manufacturer1: ViiV Healthcare Drug Class1,4: Antiretroviral Agent, Integrase Inhibitor Labeled Uses4,5: Labeled1,4: In combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and children aged 12 years and older and weighing at least 40 kg. Mechanism of Action1,2: Dolutegravir inhibits the catalytic activity of HIV integrase, which is an HIV encoded enzyme required for viral replication. Integrase is one of the three HIV-1 enzymes required for viral replication. Integration of HIV into cellular DNA is a multi-step process. First, the assembly of integrase in a stable complex with the viral DNA occurs. Second, the terminal dinucleotides from each end of the viral DNA are removed by endonucleolytic processing. Lastly, the viral DNA 3' ends are covalently linked to the cellular (target) DNA by strand transfer. The last two processes, which are catalytic, require integrase to be appropriately assembled on a specific viral DNA substrate. Inhibition of integrase by dolutegravir prevents the covalent insertion, or integration, of unintegrated linear HIV DNA into the host cell genome preventing the formation of the HIV provirus. The provirus is required to direct the production of progeny virus, so inhibiting integration prevents propagation of the viral infection. Pharmacokinetics1: Absorption: Tmax 2-3 hours Vd 17.4L T1/2 14 hours Clearance 1.0 L/h Protein Binding >98.9% Bioavailability Not established Metabolism1,2: Dolutegravir is primarily metabolized via UGT1A1 with some contribution from CYP3A. Metabolism occurs via UDP-glucuronosyltransferase (UGT)1A1 (major) and by the hepatic isoenzyme CYP3A (minor).
    [Show full text]
  • Supplementary Information
    Supplementary Information Network-based Drug Repurposing for Novel Coronavirus 2019-nCoV Yadi Zhou1,#, Yuan Hou1,#, Jiayu Shen1, Yin Huang1, William Martin1, Feixiong Cheng1-3,* 1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA 2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA 3Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA #Equal contribution *Correspondence to: Feixiong Cheng, PhD Lerner Research Institute Cleveland Clinic Tel: +1-216-444-7654; Fax: +1-216-636-0009 Email: [email protected] Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. Supplementary Table S2. Protein sequence identities across 5 protein regions in 15 coronaviruses. Supplementary Table S3. HCoV-associated host proteins with references. Supplementary Table S4. Repurposable drugs predicted by network-based approaches. Supplementary Table S5. Network proximity results for 2,938 drugs against pan-human coronavirus (CoV) and individual CoVs. Supplementary Table S6. Network-predicted drug combinations for all the drug pairs from the top 16 high-confidence repurposable drugs. 1 Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. GenBank ID Coronavirus Identity % Host Location discovered MN908947 2019-nCoV[Wuhan-Hu-1] 100 Human China MN938384 2019-nCoV[HKU-SZ-002a] 99.99 Human China MN975262
    [Show full text]
  • HIV Integrase Inhibitor Pharmacogenetics and Clinical Outcomes: an Exploratory Association Study Derek E
    East Tennessee State University Digital Commons @ East Tennessee State University Electronic Theses and Dissertations Student Works 8-2018 HIV Integrase Inhibitor Pharmacogenetics and Clinical Outcomes: An Exploratory Association Study Derek E. Murrell East Tennessee State University Follow this and additional works at: https://dc.etsu.edu/etd Part of the Other Pharmacy and Pharmaceutical Sciences Commons, Pharmacology Commons, and the Virus Diseases Commons Recommended Citation Murrell, Derek E., "HIV Integrase Inhibitor Pharmacogenetics and Clinical Outcomes: An Exploratory Association Study" (2018). Electronic Theses and Dissertations. Paper 3465. https://dc.etsu.edu/etd/3465 This Dissertation - Open Access is brought to you for free and open access by the Student Works at Digital Commons @ East Tennessee State University. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of Digital Commons @ East Tennessee State University. For more information, please contact [email protected]. HIV Integrase Inhibitor Pharmacogenetics and Clinical Outcomes: An Exploratory Association Study _____________________ A dissertation presented to the faculty of the Department of Biomedical Sciences East Tennessee State University In partial fulfillment of the requirements for the degree Doctor of Philosophy in Biomedical Sciences, Pharmaceutical Sciences Concentration _____________________ by Derek Edward Murrell August 2018 _____________________ Sam Harirforoosh, PharmD, PhD, Chair Jonathan Moorman, MD, PhD David Roane, PhD Robert Schoborg, PhD Zhi Qiang Yao, MD, PhD Keywords: Integrase Strand Transfer Inhibitor, Dolutegravir, Elvitegravir, Raltegravir, Pharmacogenetics, HIV, Renal, Hepatic, Adverse events ABSTRACT HIV Integrase Inhibitor Pharmacogenetics and Clinical Outcomes: An Exploratory Association Study by Derek Edward Murrell As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy.
    [Show full text]
  • Novel Derivatives of Bio-Affecting Phenolic Compounds and Pharmaceutical Composition Containing Them
    Europaisches Patentamt European Patent Office © Publication number: 0046 270 A1 Office europeen des brevets ™ EUROPEAN PATENT APPLICATION @ Application number: 81106277.7 © Int. CI.3: C 07 C 103/78, C 07 C 93/26, C 07 C 69/24, C 07 C 1 53/07, @ Date of filing: 12.08.81 C07C 69/28 // C07C1 25/065 <§) Priority: 13.08.80 US 177825 © Applicant: INTERx RESEARCH CORPORATION, 2201 West 21 st Street, Lawrence Kansas 66044 (US) © I nventor : Bodor, Nicholas S., 31 5 Southwest 91 st Street, ® Dateofpublicationofapplication:24.02.82 S^^S^mHariMBM Bulletin m/b Terrace, Gainesville, Florida 32605 (US) Inventor: Pogany, Stefano A., 520 Louisiana Street, Lawrence Kansas 66044 (US) @ Designated Contracting States : AT BE CH DE FR GB IT ® Representative: Abitz, Walter, Dr.-lng. et al, Abitz, Mori, LI LU NL SE Gritschneder P.O. Box 86 01 09, D-8000 Munchen 86 (DE) Novel derivatives of bio-affecting phenolic compounds and pharmaceutical composition containing them. Novel@ Novel transient prodrug forms of bio-affecting phe- amyl, CH2ONO2,CH2ON02, -CH2OCOR2 or any non-heterocyclic nolic compounds are selected from the group consisting of member of the group defined by R2Rz above; and n.isn is at least those having the structural formula (I): one and equals the total number of phenolic hydroxyl functions comprising the non-steroidal bioaffecting phenol o etherified via a R2COXCH(R3)0-moiety; those having the structural formula (II): R2-C-X-CH-0- (I) I O R, II R2-C-X-CH-0- -RM-i-O-C-R2 (II) wherein X is O, S or NR5 wherein R5 is hydrogen or lower alkyl;alky!;
    [Show full text]