lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(S(C)(=O)=O)c2)cc1-c1cc(N2CCOCC2)c(=O)n(C)c1
InChIKey: HJEAPQLJRHRRQR-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: In Vitro Enzyme Assay: Final assay conditions were 4 pM cRaf, 3 uM ATP, 10 nM biotin tagged MEK1 kinase dead protein substrate. Reactions were performed in Greiner384 well plates, catalog #784075. Reaction buffer was 50 mM Tris, pH 7.5, 50 mM NaCl, 10 mM MgCl2, 0.01% Tween-20, 0.05% BSA and 1 mM DTT. 5 ul of 2×cRaf plus MEK1 were dispensed into plates containing 0.25 ul of compound in 100% DMSO and incubated at room temperature for 30 minutes. Reactions were started by addition of 5 ul of 2×ATP. Reactions were run for two hours and terminated by addition of 10 ul of 2× antibody and Alphascreen bead mixture in Stop Buffer. Stop Buffer was 50 mM Tris, pH 7.5, 0.005% Tween-20, 25 mM EDTA.
Measurement: IC50 = 0.269 nM (pChEMBL 9.569999694824219)
Descriptors: MW 481.57, ALogP 2.85, HBA 7, HBD 1, PSA 97.71, QED 0.6
Compound (SMILES): CC(C)C[C@@H](/C=C/[N+](=O)[O-])NC(=O)[C@H](CC(C)C)NC(=O)OCc1ccccc1
InChIKey: TYDCYAYSUZPKGW-ONNQBUSKSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human cathepsin L
Measurement: Ki = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 405.5, ALogP 3.65, HBA 5, HBD 2, PSA 110.57, QED 0.43
Compound (SMILES): C=CC(=O)Nc1cccc(C2CCNc3c(C(N)=O)c(-c4ccc(Oc5ccccc5)cc4)nn32)c1
InChIKey: DWCINJSURHVICU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 479.54, ALogP 4.97, HBA 6, HBD 3, PSA 111.27, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(C(N)=O)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YXAFWGPKAAKJHB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 519.57, ALogP 3.73, HBA 9, HBD 1, PSA 121.28, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(Cc2csc(C)n2)c2ccc3ncc(-c4cnn(CCN5CCNCC5)c4)nc3c2)c1
InChIKey: KYDPEBSICGOHJT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 570.72, ALogP 4.52, HBA 11, HBD 1, PSA 93.46, QED 0.26
Compound (SMILES): O=C(NCC(O)(c1ccccc1)C(F)(F)F)[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: HRHHWOWEPUBVMN-VTBPVJSFSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 472.47, ALogP 3.45, HBA 6, HBD 3, PSA 108.2, QED 0.41
Compound (SMILES): CC(C)Oc1ccc(-c2nc(-c3cccc4c3CC[C@H]4NCC(=O)N(C)C)no2)cc1C#N.Cl
InChIKey: IANYXLDHLUODAK-ZMBIFBSDSA-N
Target: Sphingosine 1-phosphate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95977
Assay: Agonist activity at human S1P4 expressed in bla TANGO U2OS cells assessed as inhibition of cAMP formation preincubated for 4 hrs followed by FRET-based beta-lactamase fluorescent substrate addition measured after 2 hrs
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.52, ALogP 3.73, HBA 7, HBD 1, PSA 104.28, QED 0.59
Compound (SMILES): CCC(CC)CN1CCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: KYGRLSQAAKVRBS-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 519.47, ALogP 6.2, HBA 7, HBD 1, PSA 68.74, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCn2cccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XPKLWQVCOXZZKV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 455.52, ALogP 4.08, HBA 9, HBD 0, PSA 83.12, QED 0.35
Compound (SMILES): CCc1ccc(/N=C2\S/C(=C\c3ccnc(Nc4ccc(C(=O)O)cn4)c3)C(=O)N2C)cc1
InChIKey: ZJQWORQRPDYKRS-KGQWDEOMSA-N
Target: Aurora kinase C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQB9
Assay: Binding affinity to human Aurora C kinase expressed in Escherichia coli BL21 cells incubated for 1 hr by active site directed binding competition assay
Measurement: Kd = 10.8 nM (pChEMBL 7.96999979019165)
Descriptors: MW 459.53, ALogP 4.71, HBA 7, HBD 2, PSA 107.78, QED 0.51
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1cccc(-c2cnc3[nH]cc(Cl)c3c2)c1
InChIKey: QLAKLVIXUIVHNO-QPJJXVBHSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Biochemical Inhibition Assay: 1H-pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine and 5H-pyrrolo[2,3-b]pyrazine series of compounds exhibited over >100 fold selective against Janus and TEC family of kinases except for the BMX and TXK it had activity of 30 and 45 nM respectively.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 354.84, ALogP 3.94, HBA 3, HBD 2, PSA 61.02, QED 0.68
Compound (SMILES): CCOC(=O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: YVNMVJWJGAAQLE-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.5, ALogP 3.75, HBA 9, HBD 0, PSA 91.6, QED 0.38
Compound (SMILES): CN(c1ccc(C#N)c(Br)c1)[C@@H]1CCN(c2ncnc3[nH]ccc23)C1
InChIKey: XEKZNZFRNCNSEK-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzymatic Assay: JAK1/2/3 kinase assay are performed in vitro using Kit-Tyr 6 Peptide (Invitrogen, Cat. No. PV4122). TYK2 kinase assay are performed in vitro using Z′-LYTE Kinase Assay Kit-Tyr 3 Peptide (Invitrogen, Cat. No. PV3192). Recombinant human JAK1/2/3 or TYK2 catalytic domains are from Invitrogen (Cat No. PV4774/PV4210/PV3855/PV4790); All reactions (20 μL) are started by adding 2.5 μL of the testing compound in 4% DMSO solution, 5 μL of Kinase/Peptide substrate Mixture (3.2, 0.04, 0.2 or 8 μg/mL for Recombinant human JAK1/2/3 catalytic domains, 4 μM for Z-LYTE Tyr 6 peptide or Z-LYTE Tyr 3 peptide) or Phospho-Peptide solution (Invitrogen, Cat. No. PV3192, diluted with 1.33× Kinase Buffer), 2.5 μL ATP Solution (300/100/40/100 μM, JAK1/JAK2/JAK3/TYK2) or 1.33× Kinase Buffer (Invitrogen, Cat. No. PV3189, 5× diluted with distilled water). The 384-well assay plate (Corning, Cat. No. 3575) is mixed and incubated at room temperature for 1 hour. 5 μL of the Development Solution (Dilute Development Reagent A (Cat. No. PV3297) is diluted to 1/64 with Development Buffer (Cat. No. PV3127) for JAK1, JAK2 and JAK3 assay; Development Reagent A (Cat. No. PV3297) is diluted to 1/2048 with Development Buffer (Cat. No. PV3127) for TYK2 assay. The diluted Development Solution is then added to each well, mixed and incubated at room temperature for another 1 hour. The kinase reaction is then stopped by adding 5 μL of the Stop Reagent (Invitrogen, Cat. No. PV3094), and the plate is read with Wallac 1420 VICTOR3 Multilabel Counter (PerkinElmer) at 445 nm and 520 nm fluorescence. All compounds are initially tested at 8 different concentrations (1 μM down to 0.0003 μM) using a 1:3 serial dilution scheme.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 397.28, ALogP 3.31, HBA 5, HBD 1, PSA 71.84, QED 0.73
Compound (SMILES): C[C@H](Nc1ncnc2[nH]cc(F)c12)c1nc2cccc(F)c2c(=O)n1-c1cccc(OCC(F)(F)F)c1
InChIKey: JZZTVAFNHYJHPB-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Homogeneous Time Resolved Fluorescence Assay: The ability of the compounds of the present invention to inhibit the activity of four PI3K isoforms, PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ, were determined using a commercially available lipid kinase assay run in Homogeneous Time Resolved Fluorescence (HTRF) format. Assay DescriptionAssay principle: The PIP3 product is detected by displacement of biotin-PIP3 from an energy transfer complex consisting of Europium labeled anti-GST monoclonal antibody, a GST-tagged pleckstrin homology (PH) domain, biotinylated PIP3 and Streptavidin-Allophycocyanin (APC). Excitation of Europium in the complex results in an energy transfer to the APC and a fluorescent emission at 665 nm. The PIP3 product formed by PI 3-Kinase(h) activity displaces biotin-PIP3 from the complex resulting in a loss of energy transfer and thus a decrease in signal.This is a 3-step reaction: First, the kinase reaction with PIP2 substrate is carried out in the presence of ATP, and the reaction is quenched.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 516.43, ALogP 5.05, HBA 7, HBD 2, PSA 97.72, QED 0.31
Compound (SMILES): NC/C(=C/F)COc1ccc(C(N)=O)cc1
InChIKey: CUIDJRZBPVHOGV-YVMONPNESA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Recombinant SSAO/VAP-1 Inhibition Assay in Rat Fat: Abdominal fat from BALB/c mice, Wistar or Sprague Dawley rats, which are tissues enriched with SSAO/VAP-1-were surgically removed. For every gram of animal abdominal fat tissue, 1 mL of 0.1 M NaPO4 buffer (pH 7.4) was added. Tissues were homogenized using IKA Ultra-Turrax T 10 homogenizer for 3 min, homogenate was centrifuged for 15 min at 3000×g. The middle layer (clear supernatant) was removed without disturbing the top layer (high fat content) or the debris on the bottom of the tube. SSAO/VAP-1 activity was determined by checking the fluorescent signal. Km/Vmax values were determined and the fat homogenate was aliquoted and stored at −80 °C until assays were performed. Assay was performed in a similar fashion as for human SSAO/VAP-1 (Example 5) except, the substrate (benzylamine) concentrations used for mouse fat homogenate and rat fat homogenate were 80 μM and 30 μM respectively: Briefly, in a standard 96 well plate assay 50 μL of purified human SSAO/VAP-1 (0.25 μg/mL) in 0.1 M NaPO4 buffer (pH 7.4) was added into each well. Test compounds were dissolved in DMSO and tested in a Concentration Response Curve (CRC) with 4-9 data points, typically in the micromolar or nanomolar range after incubation with human SSAO/VAP-1 for 30 min at 37 °C. After 30 min incubation, 50 μL of the reaction mixture containing 600 μM benzylamine (Sigma Aldrich), 120 μM Amplex Red (Sigma Aldrich) and 1.5 U/mL horseradish peroxidase (Sigma Aldrich) prepared in 0.1 M NaPO4 buffer (pH 7.4) were added to the corresponding well. The fluorescence unit (RFU) was read every 2.5 min for 30 min at 37 °C. excitation 565 nm and emission 590 (Optima; BMG labtech). The slope of the kinetics for each well was calculated using MARS data analysis software (BMG labtech) and this value was used to deduce the IC50 value (Dotmatics).
Measurement: IC50 < 100000 nM (pChEMBL 4)
Descriptors: MW 224.24, ALogP 0.98, HBA 3, HBD 2, PSA 78.34, QED 0.78
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3C(CNC(=O)[C@@H]3CCCN3C(=O)OC)O4)cc12
InChIKey: WUDDLZILRXBAHO-MIXNXMPVSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1b (isolate Japanese) (HCV)
UniProt: P26662
Assay: ELISA-Based Assay: Measurement of inhibition by compounds was performed using the HCV replicon system. Several different replicons encoding different HCV genotypes or mutations were used. In addition, potency measurements were made using different formats of the replicon assay, including different ways of measurements and different plating formats. See Jan M. Vrolijk et al., A replicons-based bioassay for the measurement of interferons in patients with chronic hepatitis C, 110 J. VIROLOGICAL METHODS 201 (2003); Steven S. Carroll et al., Inhibition of Hepatitis C Virus RNA Replication by 2'-Modified Nucleoside Analogs, 278(14) J. BIOLOGICAL CHEMISTRY 11979 (2003). However, the underlying principles are common to all of these determinations, and are outlined below.Stable neomycin phosphotransferase encoding replicons-harboring cell lines were used, so all cell lines were maintained under G418 selection prior to the assay. Potency was determined using a cell ELISA assay with an antibody to the replicons encoded NS3/4a protease. See Caterina Trozzi et al., In Vitro Selection and Characterization of Hepatitis C Virus Serine Protease Variants Resistant to an Active-Site Peptide Inhibitor, 77(6) J. Virol. 3669 (2003).
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 798.83, ALogP 6.06, HBA 10, HBD 2, PSA 165.31, QED 0.19
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(Cc3cc4ccccc4o3)CC2)C1
InChIKey: NDRFHXUVPHBSHC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 492.59, ALogP 4.16, HBA 8, HBD 1, PSA 102.8, QED 0.38
Compound (SMILES): CN(C)[C@H]1CCN(C[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)C1
InChIKey: UHIYATACPWKMNN-JYJNAYRXSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 367.5, ALogP 2.52, HBA 6, HBD 1, PSA 65.35, QED 0.77
Compound (SMILES): N#CCC1(n2ccc(-c3ncnc4[nH]ccc34)c2)CN(C2CCN(C(=O)Nc3ccc(F)cc3F)CC2)C1
InChIKey: SMBNMMYAWCDVRU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 516.56, ALogP 4.33, HBA 6, HBD 2, PSA 105.87, QED 0.41
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3C)ncnc2cc1OCC1CN(C)CCO1
InChIKey: JRGYGHIKWBYTFJ-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human N-terminal GST His6-tagged thrombin cleavage site-fused ErbB2 kinase domain (Q679 to V1255 residues) expressed in baculovirus infected insect Sf9 cells using biotinylated poly-EY as substrate after 60 mins by alphascreen assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 463.37, ALogP 4.71, HBA 7, HBD 1, PSA 68.74, QED 0.57
Compound (SMILES): [2H]C([2H])([2H])Oc1cc(OC([2H])([2H])[2H])cc(N(CCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MLUFVERLBQGOEV-XERRXZQWSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 419.49, ALogP 3.57, HBA 8, HBD 1, PSA 85.53, QED 0.47
Compound (SMILES): N#CCCNC(=O)[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: AGZKYRXPTPBPOZ-HAQNSBGRSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 337.39, ALogP 1.91, HBA 6, HBD 2, PSA 111.76, QED 0.71
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3cncs3)c2c(=O)n1-c1ccccc1
InChIKey: VLBCDBMQYLNSLY-SFHVURJKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition Assays: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110δ/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 μg/mL). Reactions are initiated by the addition of ATP containing 10 μCi of γ-32P-ATP to a final concentration of 10 or 100 μM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 μL 1N HCl followed by 160 μL CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 531.6, ALogP 3.96, HBA 9, HBD 2, PSA 120.2, QED 0.33
Compound (SMILES): CN1CCN(C/C=C/C(=O)Nc2cc3c(Nc4ccc(Cc5ccccn5)cc4)ncnc3cn2)CC1
InChIKey: NBXCNCMWLZADMG-GQCTYLIASA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Irreversible inhibition of full length human ERBB1 autophosphorylation transfected in EGF-stimulated mouse NIH/3T3 cells incubated for 2 hrs followed by stimulation with EGF for 10 mins
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 494.6, ALogP 3.5, HBA 8, HBD 2, PSA 99.17, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(Cc2cn(CCO)nn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KFKMPCWDJDVUQL-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 486.54, ALogP 2.97, HBA 11, HBD 1, PSA 116.24, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCNC(C)(C)CF)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SXYFYNVZTYNDKV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 492.6, ALogP 4.91, HBA 8, HBD 1, PSA 77.33, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC[C@H]2CC#N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: QDLMCOSRVJITKF-FTBISJDPSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.63, ALogP 4.95, HBA 9, HBD 0, PSA 92.33, QED 0.3
Compound (SMILES): COc1ccc(-n2nc(C3CCOC3)cc2NC(=O)Nc2ccc(Oc3ccnc(Nc4ccc5[nH]ncc5c4)n3)c3ccccc23)cc1
InChIKey: ALNFKLJYTICTCF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: GSK 3α Enzyme Inhibition Assay: The inhibitory activities of compounds of the invention against the GSK 3α enzyme isoform (Invitrogen), are evaluated by determining the level of activation/phosphorylation of the target peptide. The GSK3-α protein (500 ng/mL, 2.5 uL) is mixed with the test compound (2.5 uL at either 4 ug/mL, 0.4 ug/mL, 0.04 ug/mL, or 0.004 ug/mL) for 2 hr at RT. The FRET peptide (8 uM, 2.5 uL), which is a phosphorylation target for GSK3α, and ATP (40 uM, 2.5 uL) are then added to the enzyme/compound mixture and the resulting mixture incubated for 1 hr. Development reagent (protease, 5 uL) is added for 1 hr prior to detection in a fluorescence microplate reader (Varioskan Flash, ThermoFisher Scientific).
Measurement: IC50 = 837 nM (pChEMBL 6.079999923706055)
Descriptors: MW 653.7, ALogP 7.38, HBA 10, HBD 4, PSA 153.13, QED 0.12
Compound (SMILES): COc1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1OCC1CN(C)C(C)(C)CO1
InChIKey: LTSCIXSOBYGHLC-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human N-terminal GST His6-tagged thrombin cleavage site-fused ErbB2 kinase domain (Q679 to V1255 residues) expressed in baculovirus infected insect Sf9 cells using biotinylated poly-EY as substrate after 60 mins by alphascreen assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 495.38, ALogP 5.32, HBA 7, HBD 1, PSA 68.74, QED 0.46
Compound (SMILES): O=c1cc(NC2CCN(S(=O)(=O)C(F)(F)F)CC2)c2cc(C(c3ccc(Cl)cc3)c3nccs3)ccc2[nH]1
InChIKey: NLIJQLLYUVUMPM-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding Assay: Experimental Procedure CB-2 Membrane Binding: Into Greiner V bottom polypropylene plates, hCB2-HEK293 membranes (2 ug/well final concentration) in assay buffer (50 mM Tris-HCl pH 7.4, 5 mM MgCl2 and 0.5 mg/ml (0.05%) Ultra fatty acid free BSA) were dispensed. Membranes were prepared as described in FELDER, C. C., et al., Molecular Pharmacology, 1992, pp 838-845, Vol. 42. Test compounds were then added to each well and then [3H] CP 55, 940 (0.5 nM final well concentration) in assay buffer (50 mM Tris-HCl pH 7.4, 5 mM MgCl2 and 0.5 mg/ml (0.05%) Ultra fatty acid free BSA) was added. Samples were mixed and incubated for 90 min at 30° C. in the Greiner V Bottom Polypropylene plate. After incubation, assay reagents were transferred to a blocked 384 well polypropylene filter plates. The binding reaction was stopped by filtration and washed nine times with ice cold rinse buffer. Filter plates were then dried overnight at room temperature. The next day, plate bottoms were sealed with plate tape and 15 ul MicroScint 20 was added to each well. Plates were incubated for 2 h and radioactivity was measured by Topcount.
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 583.06, ALogP 5.54, HBA 6, HBD 2, PSA 95.16, QED 0.31
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CCCCC[C@H](N1CCC(c3c(F)ccc(Cl)c3F)=CC1=O)c1cc-2ccn1
InChIKey: QGEHSULTCOSTKP-SANMLTNESA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition Assay: Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4 containing 145 mM NaCl, 5 mM KCl, and 0.1% PEG 8000 (polyethylene glycol; JT Baker or Fisher Scientific). Determinations were made using purified human Factor XIa at a final concentration of 25-200 pM (Haematologic Technologies) and the synthetic substrate S-2366 (pyroGlu-Pro-Arg-pNA; CHROMOGENIX® or AnaSpec) at a concentration of 0.0002-0.001 M.
Measurement: Ki = 6.61 nM (pChEMBL 8.180000305175781)
Descriptors: MW 595.05, ALogP 7.12, HBA 5, HBD 2, PSA 100.63, QED 0.31
Compound (SMILES): COc1cc(-c2cccc(OC(F)F)c2)c(F)cc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ccon3)ccc21
InChIKey: ANRNNOYJCDFVSP-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Time-dependent inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated with enzyme in presence of NADPH followed by substrate addition
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 557.51, ALogP 5.2, HBA 8, HBD 1, PSA 112.66, QED 0.28
Compound (SMILES): CC(C)n1nc(Cc2cccc(C(=O)CF)c2)c2c(N)ncnc21
InChIKey: WEPKWIAJJGCTLW-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: In vitro Kinase Assay: In vitro kinase assays for c-Src variants were performed in 50 mM Tris (pH 8.0), 10 mM MgCl2 and 1 mg/mL BSA. When obtaining kinetic parameters (kcat, Km) kinase and peptide substrate (IYGEFKKK) (SEQ ID NO:51) concentrations were 2 nM and 500 μM, respectively, while ATP concentrations ranged from 2000-0.655 μM. Addition of nonradioactive ATP supplemented with 32P ATP (3,000 Ci/mmol, NEN) was used to initiate kinase reactions. Time points were selected such that product formation never exceeded 10%. Reactions were quenched by spotting 3 μL quantities onto phosphocellulose sheets (P81, Whatman). Afterwards, the sheets were washed 3×5 minutes in 0.5% phosphoric acid and dried. Radioactivity was measured by phosphorimaging and recorded on a Typhoon fluorescence imager (Molecular Dynamics).
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 327.36, ALogP 2.73, HBA 6, HBD 1, PSA 86.69, QED 0.73
Compound (SMILES): CN1CCN(C/C=C/C(=O)Nc2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3cn2)CC1
InChIKey: QSGIGRAFESHIBA-NSCUHMNNSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Irreversible inhibition of full length human ERBB1 autophosphorylation transfected in EGF-stimulated mouse NIH/3T3 cells incubated for 2 hrs followed by stimulation with EGF for 10 mins
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 455.93, ALogP 3.3, HBA 7, HBD 2, PSA 86.28, QED 0.55
Compound (SMILES): CCOc1cc(N2CCC(N3CCN(CC(F)F)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: PYJDXWHQSYUUTM-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 793.87, ALogP 7.98, HBA 10, HBD 2, PSA 103.16, QED 0.12
Compound (SMILES): CCCCCCC(C)(C)c1cc(OC)c(C2=C[C@H]3CC[C@]2(CO)C3(C)C)c(OC)c1
InChIKey: ORJLSGKGXZBYAI-XHCCPWGMSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: [35S]GTPγS Binding Assay: Human CB2 expressing CHO-K1 membranes (5 μg per incubation mixture) were diluted in 50 mM Tris-HCl (pH 7.5) and 0.5 mM EDTA and added to HU compounds in a pre-mixed incubation cocktail. Final incubation concentrations were 55 mM Tris-HCl (pH 7.4), 1 mM EDTA, 100 mM NaCl, 5 mM MgCl2, 0.5% BSA, 50 μM GDP, 0.2 nM [35S]GTPγS (PerkinElmer) with varied HU compound concentration and 5 μg membrane. Incubations were continued for 60 minutes at 30° C. in a shaking water bath. Assays were terminated by addition of 2 ml ice cold wash buffer (50 mM Tris-HCl, pH 7.5 and 5 mM MgCl2) and filtration through pre-soaked GF/C filters (Whatman), followed by two further washes.
Measurement: EC50 = 26.4 nM (pChEMBL 7.579999923706055)
Descriptors: MW 414.63, ALogP 6.76, HBA 3, HBD 1, PSA 38.69, QED 0.43
Compound (SMILES): COc1cc(OC)cc(N(CCNS(C)(=O)=O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YZRSMWKLOJZVAD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 482.57, ALogP 2.73, HBA 9, HBD 1, PSA 111.47, QED 0.39
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1c1ccc(C(=O)NCCCCCCn2cccc(O)c2=S)c(F)c1
InChIKey: HYXAHECMTOFOFP-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) assessed as inhibition of fluorogenic peptide deacetylation
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 659.73, ALogP 6.86, HBA 7, HBD 2, PSA 101.6, QED 0.14
Compound (SMILES): Cc1cc(Nc2nccc(Oc3ccc(NC(=O)Nc4cc(C(C)(C)C)nn4-c4ccc(=O)n(CCO)c4)c4ccccc34)n2)cc2cn[nH]c12
InChIKey: ZFAJIINWCGZNAM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: GSK 3α Enzyme Inhibition Assay: The inhibitory activities of compounds of the invention against the GSK 3α enzyme isoform (Invitrogen), are evaluated by determining the level of activation/phosphorylation of the target peptide. The GSK3-α protein (500 ng/mL, 2.5 uL) is mixed with the test compound (2.5 uL at either 4 ug/mL, 0.4 ug/mL, 0.04 ug/mL, or 0.004 ug/mL) for 2 hr at RT. The FRET peptide (8 uM, 2.5 uL), which is a phosphorylation target for GSK3α, and ATP (40 uM, 2.5 uL) are then added to the enzyme/compound mixture and the resulting mixture incubated for 1 hr. Development reagent (protease, 5 uL) is added for 1 hr prior to detection in a fluorescence microplate reader (Varioskan Flash, ThermoFisher Scientific).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 684.76, ALogP 6.63, HBA 11, HBD 5, PSA 176.9, QED 0.11
Compound (SMILES): CC#CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: PTPSYWCHGKIOKO-BGYRXZFFSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 22.12 nM (pChEMBL 7.659999847412109)
Descriptors: MW 466.55, ALogP 4.49, HBA 7, HBD 2, PSA 107.95, QED 0.42
Compound (SMILES): CC(C)S(=O)(=O)c1ccccc1Nc1nc(N/N=C/c2ccc(F)cc2)ncc1Cl
InChIKey: STKCTXOVMCUJSB-BHGWPJFGSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met (unknown origin) using peptide as substrate after 60 mins by HTRF assay
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 447.92, ALogP 4.64, HBA 7, HBD 2, PSA 96.34, QED 0.4
Compound (SMILES): CS(=O)(=O)C1(c2nc(-c3cccc4[nH]ccc34)nc3c2OC[C@@H]2COCCN32)CCOCC1
InChIKey: DPGRLMCPNILHCM-HNNXBMFYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Luciferase-Based P450-Glo Assay: Five CYP isoforms (0.5 pmol) were tested, namely 1A2, 2C9, 2C19, 2D6 and 3A4 (each isoform was assayed in a separate assay plate). Each assay plate contained several compounds at 2 concentrations (10 uM and 1 uM), with 2 replicates at each concentration or a small number of compounds per plate in dose response by duplicate (50, 16.5, 5.4, 1.8, 0.6, 0.2, 0.066, 0.022, 0.007 uM). In addition, each assay plate contained 8 different concentrations of an isoform-specific inhibitor (Furafylline, Sulfaphenazole, N-3-benzylnirvanol, Quinidine and Ketoconazole as inhibitors of CYP 1A2, 2C9, 2C19, 2D6 and 3A4, respectively), with two replicates at each concentration. The test compounds and the reference inhibitors were tested at a final DMSO concentration of 0.5%. The assay plate included also 8 replicates a vehicle control containing 0.5% DMSO/H2O. The membranes containing the CYPs, test compound and the probe substrate were pre-incubated 10 min at 37°C. in the absence of NADPH, NADPH was then added following incubation for 60 minutes at 37°C., the reaction was terminated by the addition of Luciferin detection reagent. After 20 min incubation at 37°C., the assay plate was read in the Envision 2104 Multilable reader. Values were normalized against the control activity included for each CYP. These values were plotted against the inhibitor concentration and were fitted to a sigmoid dose-response curve by using the model sigmoidal Four-Parameter Logistc inplement for Activity baseÂ  software.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 470.55, ALogP 2.27, HBA 8, HBD 1, PSA 106.64, QED 0.62
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3)ncnc2cc1O[C@H]1CO[C@H]2[C@@H]1OC[C@@H]2OC(F)F
InChIKey: XHBINYIIFGVWSM-VNTMZGSJSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human N-terminal GST His6-tagged thrombin cleavage site-fused ErbB2 kinase domain (Q679 to V1255 residues) expressed in baculovirus infected insect Sf9 cells using biotinylated poly-EY as substrate after 60 mins by alphascreen assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 558.76, ALogP 4.95, HBA 8, HBD 1, PSA 83.96, QED 0.44
Compound (SMILES): N=C(NC(=N)N1CCN(C(=N)NC(=N)Nc2cccc(Br)c2)CC1)Nc1cccc(Br)c1
InChIKey: ZLRYRMQYXBEZIT-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Non-competitive inhibition of equine serum butyrylcholinesterase in presence of varying butyrylthiocholine iodide substrate level preincubated for 20 mins followed by substrate addition measured every 1 min for 30 mins
Measurement: Ki = 10320 nM (pChEMBL 4.989999771118164)
Descriptors: MW 564.29, ALogP 3.27, HBA 4, HBD 8, PSA 150, QED 0.21
Compound (SMILES): CCOC(=O)c1cnc(N2CCN(c3nnc(Cc4ccccc4)c(C)c3C)C[C@H]2C)nc1C(F)(F)F
InChIKey: BIAMMLFBGSGNNO-MRXNPFEDSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Displacement of radio-labeled smoothened agonist from human Smo by radio-ligand competition binding assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 514.55, ALogP 4.38, HBA 8, HBD 0, PSA 84.34, QED 0.45
Compound (SMILES): CCCCCC(=O)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)s2)cc1
InChIKey: ZNJLDHVXCHVFNI-GOSISDBHSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at human recombinant EP2 receptor expressed in HEK-EBNA cells incubated for 30 mins by cAMP accumulation assay
Measurement: EC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 429.54, ALogP 4.92, HBA 5, HBD 1, PSA 83.91, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ncccc2OC)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: SRWBBPJNBPSOFD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 534.62, ALogP 5.68, HBA 9, HBD 0, PSA 87.42, QED 0.23
Compound (SMILES): O=C(Nc1ccc(-c2c[nH]c(=O)c3ccccc23)cc1)N1CCc2ccccc21
InChIKey: FIICCIFGIGHGSR-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as ROCK inhibitors can be determined in a 30 μL assay containing 20 mM HEPES, pH 7.5, 20 mM MgCl2, 0.015% Brij-35, 4 mM DTT, 5 μM ATP and 1.5 μM peptide substrate (FITC-AHA-AKRRRLSSLRA-OH). Compounds were dissolved in DMSO so that the final concentration of DMSO was <2%, and the reaction was initiated with Rho kinase variants. After incubation, the reaction was terminated by the addition of EDTA and the phosphorylated and non-phosphorylated peptides separated using a LabChip 3000 Reader (Caliper Life Sciences). Controls consisted of assays that did not contain compound, and backgrounds consisted of assays that contained enzyme and substrate but had EDTA from the beginning of the reaction to inhibit kinase activity. Compounds were tested in dose-response format, and the inhibition of kinase activity was calculated at each concentration of compound.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 381.44, ALogP 4.79, HBA 2, HBD 2, PSA 65.2, QED 0.52
Compound (SMILES): Cc1nn(C)cc1C(=O)N1CCC2(CC1)CC2CNC(=O)N1Cc2ccncc2C1
InChIKey: IKNTWPJYFRAVKC-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Reversible inhibition of CYP2C9 in human liver microsomes using (S)-warfarin as substrate in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.51, ALogP 2.09, HBA 5, HBD 1, PSA 83.36, QED 0.84
Compound (SMILES): COc1cc(Nc2ncnc3ccc(-c4cn(CCCCCC(=O)NO)nn4)cc23)ccc1Oc1ccccc1
InChIKey: VQLJIZZYDFSRTB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild-type EGFR (unknown origin) assessed as remaining ATP level measured after 15 mins by luminescence analysis
Measurement: IC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 539.6, ALogP 5.5, HBA 10, HBD 3, PSA 136.31, QED 0.11
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(CCCN)c4)nc3c2)c1.O=C(O)C(F)(F)F
InChIKey: FTLYVYRWTXLATF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 489.62, ALogP 4, HBA 9, HBD 2, PSA 103.35, QED 0.31
Compound (SMILES): c1cnc2c(N3CCN(CCCc4ccc(OCCCN5CCCCCC5)cc4)CC3)cccc2c1
InChIKey: XHHDACAEDLRJOJ-UHFFFAOYSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Antagonist activity at adrenergic alpha1B receptor (unknown origin) expressed in Rat1 cells assessed as inhibition of phenylephrine-induced Ca2+ flux preincubated for 30 mins followed by phenylephrine addition by Fluo-4-AM-dye based FLIPR assay
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 486.7, ALogP 5.63, HBA 5, HBD 0, PSA 31.84, QED 0.35
Compound (SMILES): COc1ccc(C(=O)C2CCN([C@H]3CCN(Cc4nc5ccccc(=O)c5[nH]4)C3=O)CC2)cc1C
InChIKey: DUCZLEBAUSAZOC-NRFANRHFSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Biochemical Assay: The autoparsylation activity of the TNKS 1/2 or PARP1/2 enzymes was measured by the liquid chromatography-mass spectrometry (LC/MS) detection of nicotinamide as readout. Compound activity in inhibiting the TNKS and PARP autoparsylation was evaluated by IC50 measurements. In the compound screening assays, the reaction is composed of 5 uL of compound in 8-point serial dilutions with concentrations ranging from 0.0086 to 18.75 uM, 20 nM of purified enzyme, and 250 uM of p-NAD+ in the 1x Assay Buffer. After 60 min incubation at room temperature, the reactions were quenched by the addition of 10 uL of 5x quenching solution (20% formic acid and 500 nM [d]-nicotinamide in water). For the background control wells, 10 uL of the 5x quenching solution per well was added prior to the addition of p-NAD+. The % Inhibition was calculated as: (Control-Sample)/(Control-Background)*100. "Control" is the average value of 8 wells without compound; and "Background" is the average of 8 wells mixed with 5x quenching solution measured prior to initiation of the reaction.
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 474.56, ALogP 2.94, HBA 6, HBD 1, PSA 95.6, QED 0.55
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cncnc4)cc23)c1F
InChIKey: PDZUTJYMOJFETL-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin) using CEC as substrate after 15 mins
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 457.46, ALogP 3.68, HBA 6, HBD 2, PSA 117.7, QED 0.41
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3)ncnc2cc1O[C@H]1CO[C@H]2[C@@H]1OC[C@@H]2N1CCOCC1
InChIKey: UPTQFQIWDCTNMU-ZMUKGBGYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human N-terminal GST His6-tagged thrombin cleavage site-fused ErbB2 kinase domain (Q679 to V1255 residues) expressed in baculovirus infected insect Sf9 cells using biotinylated poly-EY as substrate after 60 mins by alphascreen assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 577.86, ALogP 4.04, HBA 9, HBD 1, PSA 87.2, QED 0.47
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(F)cc3F)C2)nnc1-c1cccnc1
InChIKey: IKSPSLCLHNNQFS-XXBNENTESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG transfected in HEK293 cells assessed as reduction in tail current by patch clamp assay
Measurement: IC50 = 2754.23 nM (pChEMBL 5.559999942779541)
Descriptors: MW 441.55, ALogP 4.52, HBA 6, HBD 0, PSA 46.84, QED 0.4
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(Br)cc4)cs3)cccc2n(C)c1=O
InChIKey: NIVMPNIOANBDGM-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 = 969.3 nM (pChEMBL 6.010000228881836)
Descriptors: MW 485.36, ALogP 3.3, HBA 7, HBD 1, PSA 85.99, QED 0.48
Compound (SMILES): Cc1cc(Nc2cc(C)c(C#N)c(NCCOc3ccncc3)n2)n[nH]1
InChIKey: MKIOKPWDAUFCOF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 < 400 nM (pChEMBL 6.3979997634887695)
Descriptors: MW 349.4, ALogP 2.92, HBA 7, HBD 3, PSA 111.54, QED 0.56