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Supplementary Table 1. in Vitro Side Effect Profiling Study for LDN/OSU-0212320. Neurotransmitter Related Steroids
Supplementary Table 1. In vitro side effect profiling study for LDN/OSU-0212320. Percent Inhibition Receptor 10 µM Neurotransmitter Related Adenosine, Non-selective 7.29% Adrenergic, Alpha 1, Non-selective 24.98% Adrenergic, Alpha 2, Non-selective 27.18% Adrenergic, Beta, Non-selective -20.94% Dopamine Transporter 8.69% Dopamine, D1 (h) 8.48% Dopamine, D2s (h) 4.06% GABA A, Agonist Site -16.15% GABA A, BDZ, alpha 1 site 12.73% GABA-B 13.60% Glutamate, AMPA Site (Ionotropic) 12.06% Glutamate, Kainate Site (Ionotropic) -1.03% Glutamate, NMDA Agonist Site (Ionotropic) 0.12% Glutamate, NMDA, Glycine (Stry-insens Site) 9.84% (Ionotropic) Glycine, Strychnine-sensitive 0.99% Histamine, H1 -5.54% Histamine, H2 16.54% Histamine, H3 4.80% Melatonin, Non-selective -5.54% Muscarinic, M1 (hr) -1.88% Muscarinic, M2 (h) 0.82% Muscarinic, Non-selective, Central 29.04% Muscarinic, Non-selective, Peripheral 0.29% Nicotinic, Neuronal (-BnTx insensitive) 7.85% Norepinephrine Transporter 2.87% Opioid, Non-selective -0.09% Opioid, Orphanin, ORL1 (h) 11.55% Serotonin Transporter -3.02% Serotonin, Non-selective 26.33% Sigma, Non-Selective 10.19% Steroids Estrogen 11.16% 1 Percent Inhibition Receptor 10 µM Testosterone (cytosolic) (h) 12.50% Ion Channels Calcium Channel, Type L (Dihydropyridine Site) 43.18% Calcium Channel, Type N 4.15% Potassium Channel, ATP-Sensitive -4.05% Potassium Channel, Ca2+ Act., VI 17.80% Potassium Channel, I(Kr) (hERG) (h) -6.44% Sodium, Site 2 -0.39% Second Messengers Nitric Oxide, NOS (Neuronal-Binding) -17.09% Prostaglandins Leukotriene, -
SUPPLEMENTARY NOTE Co-Activation of GR and NFKB
SUPPLEMENTARY NOTE Co-activation of GR and NFKB alters the repertoire of their binding sites and target genes. Nagesha A.S. Rao1*, Melysia T. McCalman1,*, Panagiotis Moulos2,4, Kees-Jan Francoijs1, 2 2 3 3,5 Aristotelis Chatziioannou , Fragiskos N. Kolisis , Michael N. Alexis , Dimitra J. Mitsiou and 1,5 Hendrik G. Stunnenberg 1Department of Molecular Biology, Radboud University Nijmegen, the Netherlands 2Metabolic Engineering and Bioinformatics Group, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece 3Molecular Endocrinology Programme, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Greece 4These authors contributed equally to this work 5 Corresponding authors E-MAIL: [email protected] ; TEL: +31-24-3610524; FAX: +31-24-3610520 E-MAIL: [email protected] ; TEL: +30-210-7273741; FAX: +30-210-7273677 Running title: Global GR and NFKB crosstalk Keywords: GR, p65, genome-wide, binding sites, crosstalk SUPPLEMENTARY FIGURES/FIGURE LEGENDS AND SUPPLEMENTARY TABLES 1 Rao118042_Supplementary Fig. 1 A Primary transcript Mature mRNA TNF/DMSO TNF/DMSO 8 12 r=0.74, p< 0.001 r=0.61, p< 0.001 ) 2 ) 10 2 6 8 4 6 4 2 2 0 Fold change (mRNA) (log Fold change (primRNA) (log 0 −2 −2 −2 0 2 4 −2 0 2 4 Fold change (RNAPII) (log2) Fold change (RNAPII) (log2) B chr5: chrX: 56 _ 104 _ DMSO DMSO 1 _ 1 _ 56 _ 104 _ TA TA 1 _ 1 _ 56 _ 104 _ TNF TNF Cluster 1 1 _ Cluster 2 1 _ 56 _ 104 _ TA+TNF TA+TNF 1 _ 1 _ CCNB1 TSC22D3 chr20: chr17: 25 _ 33 _ DMSO DMSO 1 _ 1 _ 25 _ 33 _ TA TA 1 _ 1 _ 25 _ 33 _ TNF TNF Cluster 3 1 _ Cluster 4 1 _ 25 _ 33 _ TA+TNF TA+TNF 1 _ 1 _ GPCPD1 CCL2 chr6: chr22: 77 _ 35 _ DMSO DMSO 1 _ 77 _ 1 _ 35 _ TA TA 1 _ 1 _ 77 _ 35 _ TNF Cluster 5 Cluster 6 TNF 1 _ 1 _ 77 _ 35 _ TA+TNF TA+TNF 1 _ 1 _ TNFAIP3 DGCR6 2 Supplementary Figure 1. -
A Pathobiological Role of the Insulin Receptor in Chronic Lymphocytic Leukemia
Published OnlineFirst February 9, 2011; DOI: 10.1158/1078-0432.CCR-10-2058 Clinical Cancer Human Cancer Biology Research See commentary p. 2605 A Pathobiological Role of the Insulin Receptor in Chronic Lymphocytic Leukemia Kamlai Saiya-Cork1, Roxane Collins1, Brian Parkin1, Peter Ouillette1, Erlene Kuizon1, Lisa Kujawski1, Harry Erba1, Erica Campagnaro1, Kerby Shedden2, Mark Kaminski1, and Sami N. Malek1 Abstract Purpose: The chromosomal deletion 11q affects biology and clinical outcome in chronic lymphocytic leukemia (CLL) but del11q-deregulated genes remain incompletely characterized. Experimental Design: We have employed integrated genomic profiling approaches on CLL cases with and without del11q to identify 11q-relevant genes. Results: We have identified differential expression of the insulin receptor (INSR) in CLL, including high- level INSR expression in the majority of CLL with del11q. High INSR mRNA expression in 11q CLL (10- fold higher mean levels than other genomic categories) was confirmed by quantitative PCR in 247 CLL cases. INSR protein measurements in 257 CLL cases through flow cytometry, compared with measurements þ in normal CD19 B cells and monocytes, confirmed that a subset of CLL aberrantly expresses high INSR levels. INSR stimulation by insulin in CLL cells ex vivo resulted in the activation of canonical INSR signaling pathways, including the AKT-mTOR and Ras/Raf/Erk pathways, and INSR activation partially abrogated spontaneous CLL cell apoptosis ex vivo. Higher INSR levels correlated with shorter time to first therapy and shorter overall survival (OS). In bivariate analysis, INSR expression predicted for rapid initial disease progression and shorter OS in ZAP-70–low/negative CLL. Finally, in multivariate analysis (ZAP-70 status, IgVH status, and INSR expression), we detected elevated HRs and trends for short OS for CLL cases with high INSR expression (analyzed inclusive or exclusive of cases with del11q). -
PRODUCTS and SERVICES Target List
PRODUCTS AND SERVICES Target list Kinase Products P.1-11 Kinase Products Biochemical Assays P.12 "QuickScout Screening Assist™ Kits" Kinase Protein Assay Kits P.13 "QuickScout Custom Profiling & Panel Profiling Series" Targets P.14 "QuickScout Custom Profiling Series" Preincubation Targets Cell-Based Assays P.15 NanoBRET™ TE Intracellular Kinase Cell-Based Assay Service Targets P.16 Tyrosine Kinase Ba/F3 Cell-Based Assay Service Targets P.17 Kinase HEK293 Cell-Based Assay Service ~ClariCELL™ ~ Targets P.18 Detection of Protein-Protein Interactions ~ProbeX™~ Stable Cell Lines Crystallization Services P.19 FastLane™ Structures ~Premium~ P.20-21 FastLane™ Structures ~Standard~ Kinase Products For details of products, please see "PRODUCTS AND SERVICES" on page 1~3. Tyrosine Kinases Note: Please contact us for availability or further information. Information may be changed without notice. Expression Protein Kinase Tag Carna Product Name Catalog No. Construct Sequence Accession Number Tag Location System HIS ABL(ABL1) 08-001 Full-length 2-1130 NP_005148.2 N-terminal His Insect (sf21) ABL(ABL1) BTN BTN-ABL(ABL1) 08-401-20N Full-length 2-1130 NP_005148.2 N-terminal DYKDDDDK Insect (sf21) ABL(ABL1) [E255K] HIS ABL(ABL1)[E255K] 08-094 Full-length 2-1130 NP_005148.2 N-terminal His Insect (sf21) HIS ABL(ABL1)[T315I] 08-093 Full-length 2-1130 NP_005148.2 N-terminal His Insect (sf21) ABL(ABL1) [T315I] BTN BTN-ABL(ABL1)[T315I] 08-493-20N Full-length 2-1130 NP_005148.2 N-terminal DYKDDDDK Insect (sf21) ACK(TNK2) GST ACK(TNK2) 08-196 Catalytic domain -
Brain-Restricted Mtor Inhibition with Binary Pharmacology 2 3 Ziyang Zhang1, Qiwen Fan2,3, Xujun Luo2,3, Kevin J
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.12.336677; this version posted October 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Brain-Restricted mTOR Inhibition with Binary Pharmacology 2 3 Ziyang Zhang1, Qiwen Fan2,3, Xujun Luo2,3, Kevin J. Lou1, William A. Weiss2,3,4,5, Kevan 4 M. Shokat1,* 5 6 1 Department of Cellular and Molecular Pharmacology and Howard Hughes Medical 7 Institute, University of California, San Francisco, California 8 2 Helen Diller Family Comprehensive Cancer Center, San Francisco, California 9 3 Department of Neurology, University of California, San Francisco, California 10 4 Department of Pediatrics, University of California, San Francisco, California 11 5 Department of Neurological Surgery, University of California, San Francisco, California 12 * Corresponding author. [email protected] (K.M.S.). 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.12.336677; this version posted October 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 13 Abstract 14 On-target-off-tissue drug engagement is an important source of adverse effects 15 that constrains the therapeutic window of drug candidates. In diseases of the central 16 nervous system, drugs with brain-restricted pharmacology are highly desirable. -
Supplementary Information Supplementary Table 1
Supplementary information Supplementary Table 1 Kinase Type Format N Average SD (IC50) ALK Y Lantha 6 > 10 n.d. AURORA_A S/T Caliper 6 > 10 n.d. AXL Y Lantha 3 > 10 n.d. BTK Y Caliper 6 > 10 n.d. cABL Y Caliper 4 2.0 0.38 cABLT315 Y Caliper 6 > 10 n.d. CaMK2 S/T Caliper 3 > 10 n.d. CDK2A S/T Caliper 6 > 10 n.d. CDK4D1 S/T Caliper 3 > 10 n.d. CK1 S/T Caliper 3 > 10 n.d. cKIT Y Lantha 6 > 10 n.d. cMET Y Lantha 7 > 10 n.d. COT1 S/T Caliper 4 > 10 n.d. CSK Y Lantha 2 > 10 n.d. cSRC Y Lantha 3 > 10 n.d. EphA4 Y Lantha 6 > 10 n.d. EphB4 Y Lantha 6 > 10 n.d. ERK2 S/T Caliper 6 > 10 n.d. FAK Y Lantha 3 > 10 n.d. FGFR-1 Y Lantha 3 > 10 n.d. FGFR-2 Y Lantha 3 > 10 n.d. FGFR-3 Y Lantha 3 > 10 n.d. FGFR3K650E Y Lantha 6 > 10 n.d. FGFR-4 Y Lantha 6 > 10 n.d. FLT3 Y Lantha 3 > 10 n.d. FYN Y Lantha 3 > 10 n.d. GSK3beta S/T Caliper 6 > 10 n.d. HCK Y Lantha 3 > 10 n.d. HER1 Y Lantha 6 > 10 n.d. HER2 Y Lantha 6 > 10 n.d. HER4 Y Lantha 3 > 10 n.d. IGF1R Y Lantha 6 > 10 n.d. INS1R Y Lantha 6 > 10 n.d. IRAK4 S/T Caliper 3 > 10 n.d. -
Gene Symbol Accession Alias/Prev Symbol Official Full Name AAK1 NM 014911.2 KIAA1048, Dkfzp686k16132 AP2 Associated Kinase 1
Gene Symbol Accession Alias/Prev Symbol Official Full Name AAK1 NM_014911.2 KIAA1048, DKFZp686K16132 AP2 associated kinase 1 (AAK1) AATK NM_001080395.2 AATYK, AATYK1, KIAA0641, LMR1, LMTK1, p35BP apoptosis-associated tyrosine kinase (AATK) ABL1 NM_007313.2 ABL, JTK7, c-ABL, p150 v-abl Abelson murine leukemia viral oncogene homolog 1 (ABL1) ABL2 NM_007314.3 ABLL, ARG v-abl Abelson murine leukemia viral oncogene homolog 2 (arg, Abelson-related gene) (ABL2) ACVR1 NM_001105.2 ACVRLK2, SKR1, ALK2, ACVR1A activin A receptor ACVR1B NM_004302.3 ACVRLK4, ALK4, SKR2, ActRIB activin A receptor, type IB (ACVR1B) ACVR1C NM_145259.2 ACVRLK7, ALK7 activin A receptor, type IC (ACVR1C) ACVR2A NM_001616.3 ACVR2, ACTRII activin A receptor ACVR2B NM_001106.2 ActR-IIB activin A receptor ACVRL1 NM_000020.1 ACVRLK1, ORW2, HHT2, ALK1, HHT activin A receptor type II-like 1 (ACVRL1) ADCK1 NM_020421.2 FLJ39600 aarF domain containing kinase 1 (ADCK1) ADCK2 NM_052853.3 MGC20727 aarF domain containing kinase 2 (ADCK2) ADCK3 NM_020247.3 CABC1, COQ8, SCAR9 chaperone, ABC1 activity of bc1 complex like (S. pombe) (CABC1) ADCK4 NM_024876.3 aarF domain containing kinase 4 (ADCK4) ADCK5 NM_174922.3 FLJ35454 aarF domain containing kinase 5 (ADCK5) ADRBK1 NM_001619.2 GRK2, BARK1 adrenergic, beta, receptor kinase 1 (ADRBK1) ADRBK2 NM_005160.2 GRK3, BARK2 adrenergic, beta, receptor kinase 2 (ADRBK2) AKT1 NM_001014431.1 RAC, PKB, PRKBA, AKT v-akt murine thymoma viral oncogene homolog 1 (AKT1) AKT2 NM_001626.2 v-akt murine thymoma viral oncogene homolog 2 (AKT2) AKT3 NM_181690.1 -
LANCE Ultra Kinase Assay Selection Guide
FINDING THE PATHWAY TO ASSAY OPTIMIZATION IS EASY LANCE® Ultra Kinase Assay Selection Guide LANCE Ultra Serine/Threonine Kinase Selection Guide LANCE® Ultra TR-FRET reagents comprise the widest portfolio of validated kinase assay offerings available for rapid, sensitive and robust screening of purified kinase targets in a biochemical format. • We provide S/B ratiometric data for each LANCE Ultra assay to guide you to • Our selection guides contain over 300 kinases from a variety of suppliers: the best performing solution for your assay. – 225 Serine/Threonine kinases validated on LANCE Ultra reagents • Rapid assay optimization every time. – 85 Tyrosine kinases validated on LANCE Ultra reagents How to use this guide: 1. Locate your kinase If you cannot find your kinase of interest, please ask your PerkinElmer sales • In many cases, up to three commercial kinase vendors have been tested. specialist, as our list continues to expand. Two kits are available for testing purposes: • Many common aliases are shown in parenthesis. • KinaSelect Ser/Thr kit (5 x 250 data points, TRF0300-C) 2. Best performing ULight ™ substrates are listed for each enzyme according to performance – 5 ULight-labeled Ser/Thr kinase specific substrates + 5 matching Europium-labeled anti-phospho antibodies • Signal to background (S/B) ratios (Signal at 665 nm / minus ATP control at 665 nm) are indicated in parenthesis. • KinaSelect TK kit (1,000 data points, TRF0301-D) • All S/B ratios were obtained at fixed experimental conditions unless – 1 ULight-labeled kinase specific substrate + 1 matching otherwise noted (see page 10). Europium-labeled anti-phospho antibody 3. Based on your substrate choice, find the corresponding Europium-labeled anti-phospho antibody on page 11 (i.e. -
1 a Pathobiological Role of the Insulin Receptor In
Author Manuscript Published OnlineFirst on February 9, 2011; DOI: 10.1158/1078-0432.CCR-10-2058 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. A PATHOBIOLOGICAL ROLE OF THE INSULIN RECEPTOR IN CHRONIC LYMPHOCYTIC LEUKEMIA Kamlai Saiya-Cork1, MS, Roxane Collins1, BS, Brian Parkin1, MD, Peter Ouillette1, MT (ASCP), Erlene Kuizon1, MD, Lisa Kujawski1, MD, Harry Erba1, MD, PhD, Erica Campagnaro1, MD, Kerby Shedden2, PhD, Mark Kaminski1, MD, and Sami N. Malek1,3, MD From the Department of Internal Medicine, Division of Hematology and Oncology1, and Department of Statistics2, University of Michigan, Ann Arbor, MI, USA. Running title: CLL transcriptome profiling and INSR expression Keywords: CLL, Insulin receptor, apoptosis, deletion 11q, disease progression Word Counts: Abstract: 250, Text: ~5,000 3To whom correspondence should be sent: Sami N. Malek, MD, Assistant Professor, Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor , MI 48109-0936. [email protected]. Phone: 734-763-2194. Fax: 734-647-9654. 1 Downloaded from clincancerres.aacrjournals.org on September 30, 2021. © 2011 American Association for Cancer Research. Author Manuscript Published OnlineFirst on February 9, 2011; DOI: 10.1158/1078-0432.CCR-10-2058 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. ABSTRACT Purpose: The chromosomal deletion 11q affects biology and clinical outcome in CLL but del11q-deregulated genes remain incompletely characterized. Experimental Design: We have employed integrated genomic profiling approaches upon CLL cases with and without del11q to identify 11q-relevant genes. -
Kinome Expression Profiling to Target New Therapeutic Avenues in Multiple Myeloma
Plasma Cell DIsorders SUPPLEMENTARY APPENDIX Kinome expression profiling to target new therapeutic avenues in multiple myeloma Hugues de Boussac, 1 Angélique Bruyer, 1 Michel Jourdan, 1 Anke Maes, 2 Nicolas Robert, 3 Claire Gourzones, 1 Laure Vincent, 4 Anja Seckinger, 5,6 Guillaume Cartron, 4,7,8 Dirk Hose, 5,6 Elke De Bruyne, 2 Alboukadel Kassambara, 1 Philippe Pasero 1 and Jérôme Moreaux 1,3,8 1IGH, CNRS, Université de Montpellier, Montpellier, France; 2Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium; 3CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biologi - cal Hematology, Montpellier, France; 4CHU Montpellier, Department of Clinical Hematology, Montpellier, France; 5Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany; 6Nationales Centrum für Tumorerkrankungen, Heidelberg , Ger - many; 7Université de Montpellier, UMR CNRS 5235, Montpellier, France and 8 Université de Montpellier, UFR de Médecine, Montpel - lier, France ©2020 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2018.208306 Received: October 5, 2018. Accepted: July 5, 2019. Pre-published: July 9, 2019. Correspondence: JEROME MOREAUX - [email protected] Supplementary experiment procedures Kinome Index A list of 661 genes of kinases or kinases related have been extracted from literature9, and challenged in the HM cohort for OS prognostic values The prognostic value of each of the genes was computed using maximally selected rank test from R package MaxStat. After Benjamini Hochberg multiple testing correction a list of 104 significant prognostic genes has been extracted. This second list has then been challenged for similar prognosis value in the UAMS-TT2 validation cohort. -
Supplemental Tables
JPET #237347 (suppl) Seletalisib: Characterization of a Novel, Potent, and Selective Inhibitor of PI3Kδ Rodger A Allen, Daniel C Brookings, Mark J Powell1,2, Jean Delgado, Lindsay K Shuttleworth, Mark Merriman, Ian J Fahy1,3, Roohi Tewari, John P Silva, Louise J Healy1,4, Gareth C G Davies, Breda Twomey, Rona M Cutler, Apoorva Kotian, Andrea Crosby, Gillian McCluskey, Gillian F Watt and Andrew Payne The Journal of Pharmacology and Experimental Therapeutics Supplementary Table 1. Human primary cell systems in BioMap profile System Primary human cell systems Stimulation 3C Venular endothelial cells IL-1β, TNFα and IFNγ 4H Venular endothelial cells IL-4 and histamine LPS PBMCs + venular endothelial cells TLR4 ligand SAg PBMCs + venular endothelial cells TCR ligands (1x) BE3C Bronchial epithelial cells α-IgM and TCR ligands (0.001x) CASM3C Coronary artery smooth muscle cells IL-1β, TNFα and IFNγ HDF3CGF Dermal fibroblasts IL-1β, TNFα and IFNγ IL-1β, TNFα, IFNγ, EGF, bFGF and MyoF Lung fibroblasts PDGF-BB Venular endothelial cells + M1 TNFα and TGFβ /Mphg macrophages BT B cells + PBMCs Zymosan (TLR2 ligand) 1 JPET #237347 (suppl) Supplementary Table 2A. Off-target activity: Seletalisib at a concentration of 10 µM was assessed in binding or activity assays against a panel of 239 kinase enzymes Seletalisib % inhibition of control Kinase values CAMK1 (CaMK1) -15 CDK7/cyclin H/MNAT1 17 CDK9/cyclin T1 -24 CHUK (IKK alpha) -4 DAPK1 -13 GSG2 (Haspin) -12 IRAK1 0 LRRK2 -18 NUAK1 (ARK5) -18 PI4KA (PI4K alpha) -21 PI4KB (PI4K beta) -20 PIK3C2A (PI3K-C2 -
Dissertation Submitted to the Combined Faculties for the Natural
Dissertation submitted to the Combined Faculties for the Natural Sciences and for Mathematics of the Ruperto-Carola University of Heidelberg, Germany for the degree of Doctor of Natural Sciences presented by Diplom-Biochemiker Johannes Hermle born in: Offenbach a.M., Germany Oral-examination: July 26, 2017 siRNA SCREEN FOR IDENTIFICATION OF HUMAN KINASES INVOLVED IN ASSEMBLY AND RELEASE OF HIV-1 Referees: Prof. Dr. Hans-Georg Kräusslich Prof. Dr. Dirk Grimm ii Meiner Familie iii Summary Summary The replication of the human immunodeficiency virus type 1 (HIV-1) is as yet not fully understood. In particular the knowledge of interactions between viral and host cell proteins and the understanding of complete virus-host protein networks are still imprecise. An integral picture of the hijacked cellular machinery is essential for a better comprehension of the virus. And as a prerequisite, new tools are needed for this purpose. To create such a novel tool, a screening platform for host cell factors was established in this work. The screening assay serves as a powerful method to gain insights into virus-host-interactions. It was specifically tailored to addressing the stage of assembly and release of viral particles during the replication cycle of HIV-1. It was designed to be suitable for both RNAi and chemical compound screening. The first phase of this work comprised the setup and optimization of the assay. It was shown, that it was robust and reliable and delivered reproducible results. As a subsequent step, a siRNA library targeting 724 human kinases and accessory proteins was examined. After the evaluation of the complete siRNA library in a primary screen, all primary hits were validated in a second reconfirmation screen using different siRNAs.