lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C2COC2)c1
InChIKey: ONSIKNVJAKVKOG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 10.72 nM (pChEMBL 7.96999979019165)
Descriptors: MW 417.47, ALogP 3.58, HBA 8, HBD 0, PSA 74.53, QED 0.47
Compound (SMILES): COc1cc(OCCO)cc(N(CCN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: UWEWBDWQUZMSKJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 10.96 nM (pChEMBL 7.960000038146973)
Descriptors: MW 434.5, ALogP 2.51, HBA 9, HBD 2, PSA 111.55, QED 0.41
Compound (SMILES): Cc1nc(N2Cc3cn(-c4cccc(S(C)(=O)=O)c4)nc3[C@H]2C(C)C)cc(C(F)(F)F)n1
InChIKey: IGGSXCWSHVYVMA-HXUWFJFHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 5043 nM (pChEMBL 5.300000190734863)
Descriptors: MW 465.5, ALogP 4.11, HBA 7, HBD 0, PSA 80.98, QED 0.58
Compound (SMILES): CC(C)(C)OC(=O)N1CCC(c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: PTJOSDRUWHLFGF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 342.4, ALogP 2.72, HBA 6, HBD 1, PSA 88.41, QED 0.73
Compound (SMILES): COc1cc(OC)cc(N(CC(O)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SBMUXRCSESCJIO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal His6-tagged FGFR3 expressed in insect Sf21 cells using Btn-Flt3 as substrate after 3 hrs by time resolved fluorescence assay
Measurement: IC50 = 0.7079 nM (pChEMBL 9.149999618530273)
Descriptors: MW 447.54, ALogP 4.2, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): COCCn1cc(-c2cnc3ccc(N(Cc4cc(C)no4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: SYVJHJOWIMUQMA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.82 nM (pChEMBL 8.739999771118164)
Descriptors: MW 500.56, ALogP 4.79, HBA 10, HBD 0, PSA 100.56, QED 0.27
Compound (SMILES): CC(C)Oc1ccc(Nc2nc(=O)n(CC(C)(C)C(=O)O)c(=O)n2Cc2ccc(Cl)cc2)cc1F
InChIKey: CAYYASMSWISXDA-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 504.95, ALogP 3.89, HBA 8, HBD 2, PSA 115.45, QED 0.45
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(CCCOC)cc4)cc23)c1F
InChIKey: ZMIRSJROOOVBFH-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using AMMC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 527.59, ALogP 5.47, HBA 5, HBD 2, PSA 101.15, QED 0.2
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC(=O)NCCO)c4)nc3c2)c1
InChIKey: WAKJUGXHBUNUIT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.884 nM (pChEMBL 8.539999961853027)
Descriptors: MW 502.58, ALogP 3.17, HBA 9, HBD 2, PSA 114.63, QED 0.32
Compound (SMILES): CNc1nc2ccccc2n1-c1nc2c(c(C(C)(C)S(C)(=O)=O)n1)OC[C@@H]1COCCN21
InChIKey: JEWXHIMACGOZFL-ZDUSSCGKSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
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 = 39000 nM (pChEMBL 4.409999847412109)
Descriptors: MW 458.54, ALogP 1.73, HBA 10, HBD 1, PSA 111.47, QED 0.62
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCN5CCNCC5)c4)nc3c2)c1.Cl
InChIKey: UTRCUCHWVOMQOQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.188 nM (pChEMBL 8.65999984741211)
Descriptors: MW 513.65, ALogP 3.96, HBA 9, HBD 1, PSA 80.57, QED 0.34
Compound (SMILES): O=C(O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(O)Cc2sc3ccccc3c2Cl)cc1
InChIKey: XHFNHGXDNFRXKW-JKUHXCCASA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Radioligand Binding Assay: The cell homogenate was centrifuged at 19000 r.p.m. for 20 min at 4° C. using a Beckman Ti-60 rotor. The resultant pellet was resuspended in TME buffer to give a final 1 mg/ml protein concentration, as determined by Biorad assay. Radioligand binding competition assays vs. [3H-]17-phenyl PGF2a , (5 nM) were performed in a 100 μl volume for 60 min. Binding reactions were started by adding plasma membrane fraction. The reaction was terminated by the addition of 4 ml ice-cold TRIS-HCl buffer and rapid filtration through glass fiber GF/B filters using a Brandel cell harvester. The filters were washed 3 times with ice-cold buffer and oven dried for one hour. [3H-] PGE2 (specific activity 180 Ci mmol) was used as the radioligand for EP receptors. [3H] 17-phenyl PGF2a, was employed for FP receptor binding studies. Binding studies employing EP1, EP2, EP4 and FP receptors were performed in duplicate in at least three separate experiments. A 200 μl assay volume was used. Incubations w
Measurement: Ki = 2314 nM (pChEMBL 5.639999866485596)
Descriptors: MW 469, ALogP 5.94, HBA 4, HBD 2, PSA 74.6, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(F)(F)C2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: PIOVDHZNDKMBCX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 494.55, ALogP 4.91, HBA 7, HBD 1, PSA 79.4, QED 0.35
Compound (SMILES): COc1cc(OC)c(Cl)c(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: QGTZGRJGVNFBKB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.239 nM (pChEMBL 8.649999618530273)
Descriptors: MW 481, ALogP 4.84, HBA 8, HBD 1, PSA 77.33, QED 0.37
Compound (SMILES): O=C(Nc1ccc(N2CCOCC2=O)cc1)[C@H]1C[C@@H](O)CN1C(=O)Nc1ccc(Cl)cc1
InChIKey: DMYZJLOWGSRVKP-RTBURBONSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 0 min pre-incubation of enzyme with compound and 30 min reaction time after substrate addition.
Measurement: IC50 = 1.16 nM (pChEMBL 8.9399995803833)
Descriptors: MW 458.9, ALogP 2.31, HBA 5, HBD 3, PSA 111.21, QED 0.65
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCC[C@H]2C(=O)N1
InChIKey: OEGXYNWEJSFYPO-SJCJKPOMSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 550.82, ALogP 4.28, HBA 7, HBD 2, PSA 88.61, QED 0.44
Compound (SMILES): COCCn1cc(-c2cnc3ccc(N(CC4CC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: DFRRHNQYSACYDX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (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 459.55, ALogP 4.71, HBA 8, HBD 0, PSA 74.53, QED 0.34
Compound (SMILES): COC(c1ccc(Cl)cc1)C1CCN(S(=O)(=O)c2c(C)n[nH]c2C)CC1
InChIKey: OSRKPRHWTFIMHG-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Biological Assay: The ability of a compound to block the intracellular release of calcium mediated by PK1 in RBL2H3 cells expressing human PKR1 receptors is determined as a measure of the compound's antagonist activity in vitro.Approximately 10,000 cells per assay well are seeded in normal culture medium in a 384 well plate (Corning). Twenty-four hours after seeding, the cells are loaded with a calcium sensitive fluorescent dye by replacing the culture medium with assay buffer (1× Hanks buffered saline, 25 mM HEPES, 0.1% w/v fatty acid free BSA (bovine serum albumin), pH 7.4) containing 1 mM probenecid and 1× Calcium 5 Reagent (Molecular Devices). Cells are incubated at 37° C. for 1 hour to allow for dye uptake.To test for antagonist activity, test compounds at a final concentration range between 0.32 nM-10 μM (diluted in assay buffer) are added to the assay wells and allowed to incubate for 10 minutes prior to stimulation with PK1. After incubation with test compounds the assay plate is placed in a FLIPR Tetra (Molecular Devices) and PK1 (diluted in assay buffer) is added at the determined EC80 concentration (final). Ligand-dependent changes in intracellular calcium levels are determined by measuring changes in fluorescence of the dye at 525 nM following to excitation at 485 nM.
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 397.93, ALogP 3.47, HBA 4, HBD 1, PSA 75.29, QED 0.84
Compound (SMILES): COCCN1CCCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: KZIOAIIQBIYJTQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 507.42, ALogP 4.8, HBA 8, HBD 1, PSA 77.97, QED 0.44
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(O)cc4)ccc3o2)cc1)c1ccc(O)cc1
InChIKey: RQNGIDXZVIWXLT-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human PTPN2 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 75000 nM (pChEMBL 4.119999885559082)
Descriptors: MW 537.58, ALogP 4.51, HBA 8, HBD 4, PSA 158.83, QED 0.24
Compound (SMILES): Cc1nc2c(-c3cnc[nH]3)cc(N3CCOCC3)nn2c1Cc1cccc(C(F)(F)F)c1C
InChIKey: QBFBOELIVLCBKE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta in human PC3 cells assessed as suppression of AKT phosphorylation at Ser473 after 60 mins by ELISA
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 456.47, ALogP 4.18, HBA 6, HBD 1, PSA 71.34, QED 0.5
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cc4c(=O)n(Cc5ccc(F)cc5)nnc4cc3C)cc12
InChIKey: BNSTVDKRZVYCPF-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase C316Y mutant in HCV genotype 1a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 643.67, ALogP 5.26, HBA 8, HBD 1, PSA 127.4, QED 0.25
Compound (SMILES): CNC(=O)c1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: DWYOHTOJNHEEEC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal His6-tagged FGFR3 expressed in insect Sf21 cells using Btn-Flt3 as substrate after 3 hrs by time resolved fluorescence assay
Measurement: IC50 = 2.884 nM (pChEMBL 8.539999961853027)
Descriptors: MW 428.5, ALogP 3.94, HBA 6, HBD 2, PSA 96.03, QED 0.46
Compound (SMILES): Clc1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: LMRQNYMDDPQEAJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 366.86, ALogP 3.64, HBA 5, HBD 1, PSA 62.11, QED 0.6
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cnc(N)cn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MCJMDQAWLHQTAP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 83.18 nM (pChEMBL 7.079999923706055)
Descriptors: MW 492.54, ALogP 3.61, HBA 10, HBD 1, PSA 117.1, QED 0.35
Compound (SMILES): COc1cccc(OC[C@@H]2CN(CCN3CCc4ccccc43)CCO2)c1
InChIKey: ROKNCKQMECSPFV-NRFANRHFSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Mus musculus
UniProt: Q61224
Assay: Radioligand Binding Assay: The detailed experimental protocols for the radioligand and functional receptor assays are available on the NIMH PDSP website at http://pdsp.med.unc.edu/UNC-CH %20Protocol %20Book.pdf. A. Serotonin receptors: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5A, 5-HT6 and 5-HT7. Assay Buffer: Standard Binding Buffer (50 mM Tris-HCl, 10 mM MgCl2, 1 mM EDTA, pH 7.4) Membrane Fraction Source: Transiently or stably transfected cell lines (e.g., HEK293, COS, CHO, NIH3T3). Protocol adapted from Roth et al. (1986), J. Pharmacol. Exp. Ther., 238(2): 480-485; and Roth et al. (1994), J. Pharmacol. Exp. Ther., 268(3): 1403-1410. Adrenergic Receptors: alpha1A, alpha1B, alpha2A, alpha2B, alpha2C, beta1, beta2, beta3 Assay Buffers: For alpha1 receptors, alpha1 Binding Buffer (20 mM Tris-HCl, 145 mM NaCl, pH 7.4); for alpha2 receptors, alpha2 Binding Buffer (50 mM Tris-HCl, 5 mM MgCl2, pH 7.7); for beta receptors.
Measurement: Ki = 1976 nM (pChEMBL 5.699999809265137)
Descriptors: MW 368.48, ALogP 2.84, HBA 5, HBD 0, PSA 34.17, QED 0.75
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)s2)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: MLQQTOJZLDQPMV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 8.913 nM (pChEMBL 8.050000190734863)
Descriptors: MW 522.03, ALogP 5.56, HBA 9, HBD 1, PSA 85.53, QED 0.27
Compound (SMILES): c1cc2c(ncn3nnc(C4CCCN(Cc5cncs5)C4)c23)[nH]1
InChIKey: FKXBAZKIIGGPFW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 339.43, ALogP 2.44, HBA 7, HBD 1, PSA 75, QED 0.62
Compound (SMILES): CCc1c(-c2cnc3ccc(N(CCO)c4cc(OC)cc(OC)c4)cc3n2)cnn1C
InChIKey: QMHOAFNGBZAYPM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 9.12 nM (pChEMBL 8.039999961853027)
Descriptors: MW 433.51, ALogP 3.74, HBA 8, HBD 1, PSA 85.53, QED 0.45
Compound (SMILES): Nc1cncc(-c2cn3ccnc3c(Nc3ccc(N4CCN(C5COC5)CC4)cc3)n2)n1
InChIKey: XCIGZBVOUQVIPI-UHFFFAOYSA-N
Target: CD63 antigen (SINGLE PROTEIN), Homo sapiens
UniProt: P08962
Assay: High Throughput Syk Biochemical Assay: Syk activity was measured using KinEASE (Cisbio), a time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay. In this assay, Syk-catalyzes the phosphorylation of a XL665-labeled peptide substrate. Europium conjugated phospho-tyrosine specific antibody binds the resulting phosphorylated peptide. Formation of phosphorylated peptide is quantified by TR-FRET with Europium as the donor and XL665 the acceptor in a 2-step endpoint assay. In brief, test compounds serially diluted in DMSO were delivered into Corning white, low volume, non-binding 384 well plates using the Echo 550 acoustic liquid dispenser (Labcyte®). Syk enzyme and substrates were dispensed into assay plates using a Multi-Flo (Bio-Tek Instruments). The standard 5 μL reaction mixture contained 20 μM ATP, 1 μM biotinylated peptide, 0.015 nM of Syk in reaction buffer (50 mM Hepes, pH 7.0, 0.02% NaN3, 0.1% BSA, 0.1 mM Orthovanadate, 5 mM MgCl2, 1 mM DTT, 0.025% NP-40). After 30 minutes of incubati
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 443.52, ALogP 2.03, HBA 10, HBD 2, PSA 109.73, QED 0.48
Compound (SMILES): O[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: HPMRVSRZBKQEID-KYZUINATSA-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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 257.3, ALogP 1.62, HBA 5, HBD 2, PSA 79.1, QED 0.69
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3cnn(C)c3)c2c(=O)n1-c1ccccc1
InChIKey: XUMALORDVCFWKV-IBGZPJMESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.58, ALogP 3.24, HBA 9, HBD 2, PSA 125.13, QED 0.34
Compound (SMILES): COCC(O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C(C)C)c3)nc2c1
InChIKey: WOMBJJKPVIDFFI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 477.57, ALogP 4.24, HBA 9, HBD 1, PSA 94.76, QED 0.36
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCS(C)(=O)=O)c3)nc2c1
InChIKey: NXQWBKIKMLKVOS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.571 nM (pChEMBL 8.34000015258789)
Descriptors: MW 510.62, ALogP 2.91, HBA 10, HBD 1, PSA 111.47, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H]2C[C@H]2c2ccccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JARSMEDYFYAQRJ-UQBPGWFLSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (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 492.58, ALogP 5.38, HBA 8, HBD 0, PSA 78.19, QED 0.29
Compound (SMILES): COc1cc(OC)cc(N(CC(NC(C)C)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: OKTZBKLVRWLMBJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 37.15 nM (pChEMBL 7.429999828338623)
Descriptors: MW 488.64, ALogP 5.21, HBA 8, HBD 1, PSA 77.33, QED 0.33
Compound (SMILES): CN(C)c1cccc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: ZNDKJNBPORYMQR-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 398.51, ALogP 4.64, HBA 6, HBD 0, PSA 50.08, QED 0.47
Compound (SMILES): COc1cc(OC)cc(N(CC#CC2(O)CCN(C(=O)OC(C)(C)C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.O=C(O)C(=O)O
InChIKey: NXLVPTVLMOJPJY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 190.55 nM (pChEMBL 6.71999979019165)
Descriptors: MW 598.7, ALogP 4.95, HBA 10, HBD 1, PSA 115.07, QED 0.31
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cnc(SC)nc4)cc23)c1F
InChIKey: YHJWUNOHRFFMNE-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 503.56, ALogP 4.4, HBA 7, HBD 2, PSA 117.7, QED 0.21
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JRDGKLCLEFCXSH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 12.88 nM (pChEMBL 7.889999866485596)
Descriptors: MW 476.54, ALogP 4.63, HBA 8, HBD 0, PSA 78.19, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: NRHOUXIOIPPPMR-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.778 nM (pChEMBL 8.75)
Descriptors: MW 458.57, ALogP 4.28, HBA 8, HBD 0, PSA 68.54, QED 0.39
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C2COC2)c1
InChIKey: ONSIKNVJAKVKOG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 5.129 nM (pChEMBL 8.289999961853027)
Descriptors: MW 417.47, ALogP 3.58, HBA 8, HBD 0, PSA 74.53, QED 0.47
Compound (SMILES): COc1cc(OCCO)cc(N(CCN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: UWEWBDWQUZMSKJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 10.72 nM (pChEMBL 7.96999979019165)
Descriptors: MW 434.5, ALogP 2.51, HBA 9, HBD 2, PSA 111.55, QED 0.41
Compound (SMILES): COc1cc(OC)cc(N(CC(O)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SBMUXRCSESCJIO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal His6-tagged VEGFR2 (790 end residues) expressed in baculovirus infected insect Sf21 cells using Btn-Flt3 as substrate after 1 hr by time resolved fluorescence assay
Measurement: IC50 = 190.55 nM (pChEMBL 6.71999979019165)
Descriptors: MW 447.54, ALogP 4.2, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): COCCn1cc(-c2cnc3ccc(N(Cc4cc(C)no4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: SYVJHJOWIMUQMA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.631 nM (pChEMBL 8.4399995803833)
Descriptors: MW 500.56, ALogP 4.79, HBA 10, HBD 0, PSA 100.56, QED 0.27
Compound (SMILES): CC(C)Oc1ccc(Nc2nc(=O)n(CC(C)(C)C(=O)O)c(=O)n2Cc2ccc(Cl)cc2)cc1F
InChIKey: CAYYASMSWISXDA-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 504.95, ALogP 3.89, HBA 8, HBD 2, PSA 115.45, QED 0.45
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(CCCOC)cc4)cc23)c1F
InChIKey: ZMIRSJROOOVBFH-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 527.59, ALogP 5.47, HBA 5, HBD 2, PSA 101.15, QED 0.2
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC(=O)NCCO)c4)nc3c2)c1
InChIKey: WAKJUGXHBUNUIT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.677 nM (pChEMBL 8.329999923706055)
Descriptors: MW 502.58, ALogP 3.17, HBA 9, HBD 2, PSA 114.63, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCN5CCNCC5)c4)nc3c2)c1.Cl
InChIKey: UTRCUCHWVOMQOQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 513.65, ALogP 3.96, HBA 9, HBD 1, PSA 80.57, QED 0.34
Compound (SMILES): O=C(O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(O)Cc2sc3ccccc3c2Cl)cc1
InChIKey: XHFNHGXDNFRXKW-JKUHXCCASA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Radioligand Binding Assay: The cell homogenate was centrifuged at 19000 r.p.m. for 20 min at 4° C. using a Beckman Ti-60 rotor. The resultant pellet was resuspended in TME buffer to give a final 1 mg/ml protein concentration, as determined by Biorad assay. Radioligand binding competition assays vs. [3H-]17-phenyl PGF2a , (5 nM) were performed in a 100 μl volume for 60 min. Binding reactions were started by adding plasma membrane fraction. The reaction was terminated by the addition of 4 ml ice-cold TRIS-HCl buffer and rapid filtration through glass fiber GF/B filters using a Brandel cell harvester. The filters were washed 3 times with ice-cold buffer and oven dried for one hour. [3H-] PGE2 (specific activity 180 Ci mmol) was used as the radioligand for EP receptors. [3H] 17-phenyl PGF2a, was employed for FP receptor binding studies. Binding studies employing EP1, EP2, EP4 and FP receptors were performed in duplicate in at least three separate experiments. A 200 μl assay volume was used. Incubations w
Measurement: Ki = 603 nM (pChEMBL 6.21999979019165)
Descriptors: MW 469, ALogP 5.94, HBA 4, HBD 2, PSA 74.6, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(F)(F)C2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: PIOVDHZNDKMBCX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 10.47 nM (pChEMBL 7.980000019073486)
Descriptors: MW 494.55, ALogP 4.91, HBA 7, HBD 1, PSA 79.4, QED 0.35
Compound (SMILES): COc1cc(OC)c(Cl)c(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: QGTZGRJGVNFBKB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.467 nM (pChEMBL 8.460000038146973)
Descriptors: MW 481, ALogP 4.84, HBA 8, HBD 1, PSA 77.33, QED 0.37
Compound (SMILES): O=C(Nc1ccc(N2CCOCC2=O)cc1)[C@H]1C[C@@H](O)CN1C(=O)Nc1ccc(Cl)cc1
InChIKey: DMYZJLOWGSRVKP-RTBURBONSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 0 min pre-incubation of enzyme with compound and 45 min reaction time after substrate addition.
Measurement: IC50 = 1.21 nM (pChEMBL 8.920000076293945)
Descriptors: MW 458.9, ALogP 2.31, HBA 5, HBD 3, PSA 111.21, QED 0.65
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCC[C@H]2C(=O)N1
InChIKey: OEGXYNWEJSFYPO-SJCJKPOMSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 550.82, ALogP 4.28, HBA 7, HBD 2, PSA 88.61, QED 0.44
Compound (SMILES): COCCn1cc(-c2cnc3ccc(N(CC4CC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: DFRRHNQYSACYDX-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 absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 459.55, ALogP 4.71, HBA 8, HBD 0, PSA 74.53, QED 0.34
Compound (SMILES): COC(c1ccc(Cl)cc1)C1CCN(S(=O)(=O)c2c(C)n[nH]c2C)CC1
InChIKey: OSRKPRHWTFIMHG-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Biological Assay: The ability of a compound to block the intracellular release of calcium mediated by PK1 in RBL2H3 cells expressing human PKR1 receptors is determined as a measure of the compound's antagonist activity in vitro.Approximately 10,000 cells per assay well are seeded in normal culture medium in a 384 well plate (Corning). Twenty-four hours after seeding, the cells are loaded with a calcium sensitive fluorescent dye by replacing the culture medium with assay buffer (1× Hanks buffered saline, 25 mM HEPES, 0.1% w/v fatty acid free BSA (bovine serum albumin), pH 7.4) containing 1 mM probenecid and 1× Calcium 5 Reagent (Molecular Devices). Cells are incubated at 37° C. for 1 hour to allow for dye uptake.To test for antagonist activity, test compounds at a final concentration range between 0.32 nM-10 μM (diluted in assay buffer) are added to the assay wells and allowed to incubate for 10 minutes prior to stimulation with PK1. After incubation with test compounds the assay plate is placed in a FLIPR Tetra (Molecular Devices) and PK1 (diluted in assay buffer) is added at the determined EC80 concentration (final). Ligand-dependent changes in intracellular calcium levels are determined by measuring changes in fluorescence of the dye at 525 nM following to excitation at 485 nM.
Measurement: IC50 = 4620 nM (pChEMBL 5.329999923706055)
Descriptors: MW 397.93, ALogP 3.47, HBA 4, HBD 1, PSA 75.29, QED 0.84
Compound (SMILES): COCCN1CCCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: KZIOAIIQBIYJTQ-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 507.42, ALogP 4.8, HBA 8, HBD 1, PSA 77.97, QED 0.44
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(O)cc4)ccc3o2)cc1)c1ccc(O)cc1
InChIKey: RQNGIDXZVIWXLT-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 537.58, ALogP 4.51, HBA 8, HBD 4, PSA 158.83, QED 0.24
Compound (SMILES): Cc1nc2c(-c3cnc[nH]3)cc(N3CCOCC3)nn2c1Cc1cccc(C(F)(F)F)c1C
InChIKey: QBFBOELIVLCBKE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta in human PC3 cells assessed as suppression of AKT phosphorylation at Thr308 after 60 mins by ELISA
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 456.47, ALogP 4.18, HBA 6, HBD 1, PSA 71.34, QED 0.5
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cc4c(=O)n(Cc5ccc(F)cc5)nnc4cc3C)cc12
InChIKey: BNSTVDKRZVYCPF-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase S365A mutant in HCV genotype 1a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 16.3 nM (pChEMBL 7.789999961853027)
Descriptors: MW 643.67, ALogP 5.26, HBA 8, HBD 1, PSA 127.4, QED 0.25
Compound (SMILES): CNC(=O)c1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: DWYOHTOJNHEEEC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal His6-tagged VEGFR2 (790 end residues) expressed in baculovirus infected insect Sf21 cells using Btn-Flt3 as substrate after 1 hr by time resolved fluorescence assay
Measurement: IC50 = 120.23 nM (pChEMBL 6.920000076293945)
Descriptors: MW 428.5, ALogP 3.94, HBA 6, HBD 2, PSA 96.03, QED 0.46
Compound (SMILES): Clc1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: LMRQNYMDDPQEAJ-UHFFFAOYSA-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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 366.86, ALogP 3.64, HBA 5, HBD 1, PSA 62.11, QED 0.6
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cnc(N)cn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MCJMDQAWLHQTAP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 70.79 nM (pChEMBL 7.150000095367432)
Descriptors: MW 492.54, ALogP 3.61, HBA 10, HBD 1, PSA 117.1, QED 0.35
Compound (SMILES): COc1cccc(OC[C@@H]2CN(CCN3CCc4ccccc43)CCO2)c1
InChIKey: ROKNCKQMECSPFV-NRFANRHFSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Mus musculus
UniProt: P35363
Assay: Radioligand Binding Assay: The detailed experimental protocols for the radioligand and functional receptor assays are available on the NIMH PDSP website at http://pdsp.med.unc.edu/UNC-CH %20Protocol %20Book.pdf. A. Serotonin receptors: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5A, 5-HT6 and 5-HT7. Assay Buffer: Standard Binding Buffer (50 mM Tris-HCl, 10 mM MgCl2, 1 mM EDTA, pH 7.4) Membrane Fraction Source: Transiently or stably transfected cell lines (e.g., HEK293, COS, CHO, NIH3T3). Protocol adapted from Roth et al. (1986), J. Pharmacol. Exp. Ther., 238(2): 480-485; and Roth et al. (1994), J. Pharmacol. Exp. Ther., 268(3): 1403-1410. Adrenergic Receptors: alpha1A, alpha1B, alpha2A, alpha2B, alpha2C, beta1, beta2, beta3 Assay Buffers: For alpha1 receptors, alpha1 Binding Buffer (20 mM Tris-HCl, 145 mM NaCl, pH 7.4); for alpha2 receptors, alpha2 Binding Buffer (50 mM Tris-HCl, 5 mM MgCl2, pH 7.7); for beta receptors.
Measurement: Ki = 1399 nM (pChEMBL 5.849999904632568)
Descriptors: MW 368.48, ALogP 2.84, HBA 5, HBD 0, PSA 34.17, QED 0.75
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)s2)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: MLQQTOJZLDQPMV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 8.913 nM (pChEMBL 8.050000190734863)
Descriptors: MW 522.03, ALogP 5.56, HBA 9, HBD 1, PSA 85.53, QED 0.27
Compound (SMILES): c1cc2c(ncn3nnc(C4CCCN(Cc5cncs5)C4)c23)[nH]1
InChIKey: FKXBAZKIIGGPFW-UHFFFAOYSA-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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 339.43, ALogP 2.44, HBA 7, HBD 1, PSA 75, QED 0.62
Compound (SMILES): CCc1c(-c2cnc3ccc(N(CCO)c4cc(OC)cc(OC)c4)cc3n2)cnn1C
InChIKey: QMHOAFNGBZAYPM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 16.98 nM (pChEMBL 7.769999980926514)
Descriptors: MW 433.51, ALogP 3.74, HBA 8, HBD 1, PSA 85.53, QED 0.45
Compound (SMILES): Nc1cncc(-c2cn3ccnc3c(Nc3ccc(N4CCN(C5COC5)CC4)cc3)n2)n1
InChIKey: XCIGZBVOUQVIPI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK (unknown origin) using XL665-labeled peptide as substrate in presence of ATP measured after 30 mins by TR-FRET assay
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 443.52, ALogP 2.03, HBA 10, HBD 2, PSA 109.73, QED 0.48
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3cnn(C)c3)c2c(=O)n1-c1ccccc1
InChIKey: XUMALORDVCFWKV-IBGZPJMESA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Binding affinity to human recombinant full length N-terminal GST-tagged PI3K p110delta/p85alpha coexpressed in baculovirus infected Sf9 insect cells by equilibrium fluorescence titration analysis
Measurement: Kd = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 528.58, ALogP 3.24, HBA 9, HBD 2, PSA 125.13, QED 0.34
Compound (SMILES): COCC(O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C(C)C)c3)nc2c1
InChIKey: WOMBJJKPVIDFFI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.778 nM (pChEMBL 8.75)
Descriptors: MW 477.57, ALogP 4.24, HBA 9, HBD 1, PSA 94.76, QED 0.36
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCS(C)(=O)=O)c3)nc2c1
InChIKey: NXQWBKIKMLKVOS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.631 nM (pChEMBL 8.4399995803833)
Descriptors: MW 510.62, ALogP 2.91, HBA 10, HBD 1, PSA 111.47, QED 0.33