lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): BrC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: SUNXMHYYMAXRJE-MGCOHNPYSA-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 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 334.22, ALogP 3.27, HBA 4, HBD 1, PSA 58.87, QED 0.73
Compound (SMILES): CCC(O)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)s2)cc1
InChIKey: CQNLDPUJXLNMDP-LDCVWXEPSA-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 = 312 nM (pChEMBL 6.510000228881836)
Descriptors: MW 389.47, ALogP 3.6, HBA 5, HBD 2, PSA 87.07, QED 0.72
Compound (SMILES): Cc1ccnc(-n2nnc3c2CCN(C(=O)c2cccc(C(F)(F)F)c2Cl)C3C)n1
InChIKey: NNUKCIPJCGVOKK-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding: Human or rat P2X7-1321 N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5×)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (Ki) of the test compounds.
Measurement: IC50 = 12691 nM (pChEMBL 4.900000095367432)
Descriptors: MW 436.83, ALogP 3.8, HBA 6, HBD 0, PSA 76.8, QED 0.61
Compound (SMILES): Cc1cncc(-c2cc3c(cn2)cnn3-c2ccc(=O)n([C@H]3CCCNC3)n2)n1
InChIKey: ANAOYTVZYSRWRF-HNNXBMFYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Kinase Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.PIM reactions were carried out in a final volume of 10 uL per well in a 384-well plate. A standard enzymatic reaction, initiated by the addition of 5 uL 2Ã¿Â¿ATP and test compound to 5 uL of 2x enzyme and FAM-peptide, contained 20 uM PIM1, 50 uM PIM2, or 55 uM PIM3, 1 uM FAM-peptide, and 10 uM ATP, in Reaction Buffer. After 90 minutes of incubation at room temperature, the phosphorylation reaction was stopped by the addition of 10 uL Termination Buffer. The product and substrate in each independent reaction were separated on a 12-sipper microfluidic chip (Caliper Life Sciences, Hopkinton, Mass.) run on a Caliper LC3000 (Caliper Life Sciences, Hopkinton, Mass.). The separation of product and substrate was optimized by choosing voltages and pressure using Caliper's Optimizer software (Hopkinton, Mass.). The separation conditions used a downstream voltage of -500V, an upstream voltage of -2150V, and a screening pressure of -1.2 psi. The product and substrate fluorophore were excited at 488 nm and detected at 530 nm. Substrate conversion was calculated from the electropherogram using HTS Well Analyzer software (Caliper Life Sciences, Hopkinton, Mass.). Ki values for the test compound were calculated.
Measurement: Ki = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 388.44, ALogP 1.67, HBA 9, HBD 1, PSA 103.41, QED 0.57
Compound (SMILES): CCc1c(-c2cnc3ccc(N(CCNC(C)C)c4cc(OC)cc(OC)c4)cc3n2)cnn1C.Cl
InChIKey: DTLAIVUWXPJAMT-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (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 = 9549.93 nM (pChEMBL 5.019999980926514)
Descriptors: MW 474.61, ALogP 4.75, HBA 8, HBD 1, PSA 77.33, QED 0.36
Compound (SMILES): c1ccc2cc(NC3=NC[C@@]4(CN5CCC4CC5)O3)ncc2c1
InChIKey: ZDTPXUKLGIDOCS-SFHVURJKSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Agonist activity at rat alpha3beta4 nAChR expressed in HEK293 cells for 2 mins by FLIPR assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 308.39, ALogP 2.5, HBA 5, HBD 1, PSA 49.75, QED 0.88
Compound (SMILES): COC(=O)CCCN/C=C1\C(=O)C(O)=C(C(C)C)c2cc(C)c(-c3c(C)cc4c(c3O)/C(=C/NCCCC(=O)OC)C(=O)C(O)=C4C(C)C)c(O)c21
InChIKey: IHQIQZBZMBBHBD-MFYXSQMNSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of FAM-Bid binding to human BCL2 expressed in Escherichia coli BL21 after 30 mins by fluorescence polarization assay
Measurement: Ki = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 716.83, ALogP 6.16, HBA 12, HBD 6, PSA 191.72, QED 0.08
Compound (SMILES): COc1cc(OC)cc(N(CCNC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YEKLQWUGOHZIQV-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (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 444.54, ALogP 3.94, HBA 8, HBD 1, PSA 77.33, QED 0.42
Compound (SMILES): CN1CCN(c2ccc(NC(=O)Nc3ccc(Cl)c(Cl)c3)cc2)CC1
InChIKey: IEQHSQHHGZSIPY-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Biochemical JAK and Tyk2 Kinase Assays: A panel of four LanthaScreen JAK biochemical assays (JAK1, 2, 3 and Tyk2) were carried in a common kinase reaction buffer (50 mM HEPES, pH 7.5, 0.01% Brij-35, 10 mM MgCl2, and 1 mM EGTA). Recombinant GST-tagged JAK enzymes and a GFP-tagged STAT1 peptide substrate were obtained from Life Technologies. Serially or discretely diluted compounds were pre-incubated with each of the four JAK enzymes and the substrate in white 384-well microplates (Corning) at ambient temperature for 1 h. ATP was subsequently added to initiate the kinase reactions in 10 μL total volume, with 1% DMSO. The final enzyme concentrations for JAK1, 2, 3 and Tyk2 are 4.2 nM, 0.1 nM, 1 nM, and 0.25 nM respectively; the corresponding Km ATP concentrations used are 25 μM, 3 μM, 1.6 μM, and 10 μM; while the substrate concentration is 200 nM for all four assays. Kinase reactions were allowed to proceed for 1 hour at ambient temperature before a 10 μL preparation of EDTA (10 mM final concentration) and Tb-anti-pSTAT1 (pTyr701) antibody (Life Technologies, 2 nM final concentration) in TR-FRET dilution buffer (Life Technologies) was added. The plates were allowed to incubate at ambient temperature for 1 h before being read on the EnVision reader (Perkin Elmer). Emission ratio signals (520 nm/495 nm) were recorded and utilized to calculate the percent inhibition values based on DMSO and background controls.For dose-response analysis, percent inhibition data were plotted vs. compound concentrations, and IC50 values were determined from a 4-parameter robust fit model with the Prism software (GraphPad Software). Results were expressed as pIC50 (negative logarithm of IC50) and subsequently converted to pKi (negative logarithm of dissociation constant, Ki) using the Cheng-Prusoff equation.
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 379.29, ALogP 4.39, HBA 3, HBD 2, PSA 47.61, QED 0.83
Compound (SMILES): C=CC(=O)Nc1cccc(-c2cnc3[nH]cc(-c4cccc(C(=O)OCC)c4)c3c2)c1
InChIKey: GSFPDICSPWRBBE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
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 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 411.46, ALogP 5.2, HBA 4, HBD 2, PSA 84.08, QED 0.34
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1cnc2ccccc2c1=O
InChIKey: TVJRDCQUZMGBAB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human RamosB cells assessed as suppression of BCR/anti-IgM stimulated calcium flux pre-incubated for 1 hr followed by BCR/anti-IgM stimulation
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 502.57, ALogP 5.32, HBA 5, HBD 3, PSA 114, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3cccc(C(F)(F)F)c3F)CC2)C1
InChIKey: JRPICXXMNCABMU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 567.55, ALogP 4.6, HBA 7, HBD 2, PSA 118.76, QED 0.34
Compound (SMILES): COc1cc(N2CCC(CCS(C)(=O)=O)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: RNICSIBFPJOYHB-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 737.83, ALogP 7.39, HBA 10, HBD 2, PSA 130.82, QED 0.14
Compound (SMILES): [2H]C([2H])([2H])Oc1cc(OC([2H])([2H])[2H])cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C([2H])([2H])C([2H])([2H])NC(C)C)c1
InChIKey: OLAHOMJCDNXHFI-RCEBUFFYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (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 446.56, ALogP 4.18, HBA 8, HBD 1, PSA 77.33, QED 0.41
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN(CCOCCO)CCO1
InChIKey: VDNKDMALAXYLFZ-UHFFFAOYSA-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 523.42, ALogP 3.78, HBA 9, HBD 2, PSA 98.2, QED 0.36
Compound (SMILES): CNC(=O)c1cc(F)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RFXLZLOSWGJUJY-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (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 430.49, ALogP 4.08, HBA 6, HBD 1, PSA 75.94, QED 0.5
Compound (SMILES): O=C(c1c(F)ccc(NS(=O)(=O)c2cc(F)ccc2F)c1F)c1c[nH]c2ncc(Cl)cc12
InChIKey: QNOHLXTXYALHSG-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 483.83, ALogP 4.8, HBA 4, HBD 2, PSA 91.92, QED 0.31
Compound (SMILES): COc1cc(F)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: IFLIEMPAHJDKDK-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (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 446.53, ALogP 4.79, HBA 6, HBD 1, PSA 70.17, QED 0.42
Compound (SMILES): O=C(O)C12CCC(C(=O)N3CC[C@](c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4)(S(=O)(=O)c4ccc(F)cc4)C3)(CC1)OC2
InChIKey: BVABKVKAEGWJRT-STEQJIOHSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Transactivation of human GAL4-fused LXRbeta expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 655.56, ALogP 5.43, HBA 5, HBD 1, PSA 100.98, QED 0.33
Compound (SMILES): CC1(OC(=O)N2CCC3(CC2)C[C@@H]3CNC(=O)N2Cc3ccncc3C2)COC1
InChIKey: QFORHKAMQGBXQZ-QGZVFWFLSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Reversible inhibition of CYP2D6 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 400.48, ALogP 2.13, HBA 5, HBD 1, PSA 84, QED 0.84
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(-c2ccncc2)cs1
InChIKey: VRXGZDANOSIHSR-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 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 510.41, ALogP 6.79, HBA 8, HBD 1, PSA 82.05, QED 0.26
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3C4)cc12
InChIKey: RVZDCFXTAGDKKA-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase C316Y mutant in HCV genotype 1A infected in HuH7 cells after 40 hrs by Taqman probe based RT-PCR analysis
Measurement: EC50 = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 598.63, ALogP 6.18, HBA 6, HBD 1, PSA 97.44, QED 0.26
Compound (SMILES): Cc1c(Cc2c(CNCCS(C)(=O)=O)nc3c(N)cc(N4CCOCC4)nn23)cccc1C(F)(F)F
InChIKey: GWFUHMDGIDDKAR-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 = 186 nM (pChEMBL 6.730000019073486)
Descriptors: MW 526.59, ALogP 2.2, HBA 9, HBD 2, PSA 114.85, QED 0.43
Compound (SMILES): Cc1cc(F)c(C(=O)Nc2cccc(-c3nncn3C(C)C)n2)cc1-n1cnc(C2CC2)c1
InChIKey: YIDDLAAKOYYGJG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Inhibition of human full length recombinant ASK1 using STK-Substrate-3 biotin as substrate in presence of ATP measured after 2 hrs by HTRP kinase assay
Measurement: IC50 = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 445.5, ALogP 4.68, HBA 7, HBD 1, PSA 90.52, QED 0.47
Compound (SMILES): N#Cc1cnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4ccccc4)c3F)c2c1
InChIKey: LZPYPWMVRFVWBG-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 438.42, ALogP 3.74, HBA 5, HBD 2, PSA 115.71, QED 0.46
Compound (SMILES): COc1cc(Nc2ccc(S(=O)(=O)NCC3CCCO3)c(C(F)(F)F)c2)cc(OC)c1
InChIKey: CPPNFVSJYCMUPR-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding Assay: The binding assays were performed by testing the ability of the new compounds to displace the radiolabeled synthetic non-selective cannabinoid agonist [3H]CP55940 (168 Ci/mmol; PerkinElmer) from the human CB1 (hCB1) or human CB2 (hCB2) receptors on membranes derived from stably transfected HEK-293 cells (PerkinElmer). Membranes were diluted in assay buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM MgCl2, 1 mg/ml BSA, pH=7.4). The amount of membrane was determined for each batch of membranes according to protein binding assay. The minimum amount of membrane that gave 50% specific binding was used for the binding assay. In most assays, binding was tested using 8 μg and 4 μg protein of hCB1 and hCB2 membranes, respectively. The tested compounds were dissolved in DMSO and diluted in assay buffer to a final concentration of 0.1% solvent. Total binding of [3H]CP55940 was evaluated with 1.5 nM to hCB1 and with 0.5 nM to hCB2, according to Kd affinity of [3H]CP55940 for the respective membranes. The ability of the tested compounds to displace [3H]CP55940 was evaluated first at a single concentration point of 100 nM for binding toward hCB2 or hCB1. In certain cases, the displacement was tested at compound concentrations ranging from 0.03 nM to 10 μM. Non-specific binding was measured by the addition of 1 μM of unlabelled CP55940 to the tubes. Binding assays were performed in triplicate in a total volume of 500 μl for 60 minutes at 30° C., in a shaking bath. Free and bound radioligands were separated by rapid filtration through GF/C filter plates (PerkinElmer) that had been presoaked with 0.1% Polyethylenimine (Sigma). Filters were shaken for 1 hour in 7 ml scintillation fluid (PerkinElmer) and radioactivity was determined by liquid scintillation counter (Wallac; PerkinElmer).
Measurement: Ki = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 460.47, ALogP 3.92, HBA 6, HBD 2, PSA 85.89, QED 0.62
Compound (SMILES): CC1(O)CCC(NC(=O)c2cnn3ccc(N4CCC[C@@H]4c4cc(F)ccc4F)nc23)CC1
InChIKey: CYJPVTPYPTUQAC-HYSRAYMDSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 4 nM Jak2 in a total volume of 20 μL. Human Jak2 kinase domain comprising amino acids 808-1132 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV4210).
Measurement: IC50 = 418 nM (pChEMBL 6.380000114440918)
Descriptors: MW 455.51, ALogP 3.77, HBA 6, HBD 2, PSA 82.76, QED 0.63
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccc(C#N)cc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HVEVXOZVOPQEHH-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 = 218.78 nM (pChEMBL 6.659999847412109)
Descriptors: MW 500.56, ALogP 5.11, HBA 8, HBD 0, PSA 89.09, QED 0.3
Compound (SMILES): FC(F)(F)c1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: WFPPWRAUXJMGTG-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 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 400.41, ALogP 4, HBA 5, HBD 1, PSA 62.11, QED 0.56
Compound (SMILES): CNC(=O)C[C@H]1COc2cc(F)ccc2N1C(=O)c1ccc2c(c1)NC(=O)CO2
InChIKey: MBKYLPOPYYLTNW-ZDUSSCGKSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Antagonist activity at full length human mineralocorticoid receptor expressed in human U2OS cells by luciferase reporter gene assay
Measurement: IC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 399.38, ALogP 1.7, HBA 5, HBD 2, PSA 96.97, QED 0.82
Compound (SMILES): CCN(CC)CCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: ZMEWJQRHELGMRY-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 = 1.622 nM (pChEMBL 8.789999961853027)
Descriptors: MW 460.58, ALogP 4.53, HBA 8, HBD 0, PSA 68.54, QED 0.34
Compound (SMILES): COc1cccc(-n2c([C@H](C)Nc3ncnc(N)c3C#Cc3ncccc3F)nc3cccc(Cl)c3c2=O)c1C
InChIKey: JPAOGSNPPDFDOS-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: PI3K isoforms were assayed under initial rate conditions in the presence of 25 mM Hepes (pH 7.4), and 2xKm ATP (100-300 uM), 10 uM PIP2, 5% glycerol, 5 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, 1% (v/v) DMSO at the following concentrations for each isoform: PI3K alpha, beta, delta, and gamma at 50 picomolar (pM) and PI3Kgamma at 2 nanomolar (nM). After an assay reaction time of 30 minutes at 25° C., reactions were terminated with a final concentration of 10 mM EDTA, 10 nM labeled-PIP3, and 35 nM Europium labeled GRP-1 detector protein before reading TR-FRET on an Envision plate reader (Ex: 340 nm; Em: 615/665 nm; 100 us delay and 500 us read window).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 556, ALogP 4.84, HBA 9, HBD 2, PSA 120.84, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(CO)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PYQPSJDRRIQAPP-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 = 1.95 nM (pChEMBL 8.710000038146973)
Descriptors: MW 502.62, ALogP 3.89, HBA 9, HBD 1, PSA 88.77, QED 0.37
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(OCCN5CCOCC5)nc4)cc23)c1F
InChIKey: LNZFADSEFQSOLF-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 585.63, ALogP 4, HBA 8, HBD 2, PSA 126.51, QED 0.25
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@H]1CN2CCC[C@@H]2CO1
InChIKey: FSJDACURTSWGHC-HZPDHXFCSA-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 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 475.38, ALogP 4.93, HBA 7, HBD 1, PSA 68.74, QED 0.54
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN2CSC[C@H]2CO1
InChIKey: RFGYFZFUMBQSCW-GICMACPYSA-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 493.42, ALogP 4.84, HBA 8, HBD 1, PSA 68.74, QED 0.52
Compound (SMILES): COc1cc(OC)cc(N(CCNC2CCN(S(N)(=O)=O)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RDIKEQDHARQJCT-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 = 4.266 nM (pChEMBL 8.369999885559082)
Descriptors: MW 566.69, ALogP 2.44, HBA 10, HBD 2, PSA 140.73, QED 0.3
Compound (SMILES): O=C(CCCCCCOc1ccc2cc1COC/C=C/COCc1cccc(c1)-c1ccnc(n1)N2)NO
InChIKey: IYBYMTCQQMFOHB-AATRIKPKSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of human recombinant N-terminal His-tagged HDAC11 (1 to 347 residues) expressed in baculovirus infected insect cells preincubated with enzyme followed by fluorogenic Arg-His-Lys-Lys(Ac)-AMC substrate addition measured after 2 hrs by fluorescence assay relative to control
Measurement: IC50 = 930 nM (pChEMBL 6.03000020980835)
Descriptors: MW 518.61, ALogP 5.32, HBA 8, HBD 3, PSA 114.83, QED 0.16
Compound (SMILES): N#CC1(NC(=O)[C@@H]2Cc3ccc(c(Cl)c3)OCCCCOc3cc(C(F)(F)F)ccc3C(=O)N2)CC1
InChIKey: XAPRSGPLBWSEHV-IBGZPJMESA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 521.92, ALogP 4.42, HBA 5, HBD 2, PSA 100.45, QED 0.61
Compound (SMILES): CCN(CC)C(=O)c1ccc2cc1CN(C)C(=O)[C@H](Nc1ccc3c(N)nccc3c1)c1ccc(c(C)c1)[C@@H](C)COC(=O)N2
InChIKey: KHVYVAAEFVFJSL-WKRVVKTRSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P13726
Assay: Inhibition of full-length human TF/recombinant human factor 7a assessed as decrease in conversion of factor 10 to factor 10a by measuring S2765 hydrolysis after 15 mins
Measurement: Ki = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 608.74, ALogP 6.08, HBA 7, HBD 3, PSA 129.89, QED 0.25
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2c(F)ccc(Cl)c2c(=O)n1-c1cncc(F)c1
InChIKey: DHEKIAITWHNQAM-QMMMGPOBSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human whole blood assessed as reduction in anti-FCepsilonR1 mAb-stimulated basophil activation preincubated for 60 mins followed by anti-FCepsilonR1 mAb stimulation and measured after 25 mins by flow cytometry analysis
Measurement: EC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 469.84, ALogP 2.71, HBA 10, HBD 3, PSA 161.42, QED 0.41
Compound (SMILES): C=CC(=O)Nc1ccccc1C1CCNc2c(C(N)=O)c(-c3ccc(Oc4ccccc4)cc3)nn21
InChIKey: TZAAHFAAEVJUJO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Kinase Assay: Compounds disclosed herein were tested for inhibition of Btk kinase activity in an assay based on time-resolved fluorescence resonance energy transfer methodology. Recombinant Btk was pre-incubated with the compounds disclosed herein at room temperature for 1 hour in an assay buffer containing 50 mM Tris pH7.4, 10 mM MgCl2, 2 mM MnCl2, 0.1 mM EDTA, 1 mM DTT, 20 nM SEB, 0.1% BSA, 0.005% tween-20. The reactions were initiated by the addition of ATP (at the concentration of ATP Km) and peptide substrate (Biotin-AVLESEEELYSSARQ-NH2). After incubating at room temperature for 1 h. an equal volume of stop solution containing 50 mM HEPES pH7.0, 800 mM KF, 20 mM EDTA, 0.1% BSA, Eu cryptate-conjugated p-Tyr66 antibody and streptavidin-labeled XL665 was added to stop the reaction. Plates were further incubated at room temperature for 1 hour, and then the TR-FRET signals (ex337 nm, em 620 nm/665 nm) were read on BMG PHERAstar FS instrument. The residual enzyme activity in presence of increasing concentrations of compounds was calculated based on the ratio of fluorescence at 615 nm to that at 665 nm. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software.
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 479.54, ALogP 4.97, HBA 6, HBD 3, PSA 111.27, QED 0.32
Compound (SMILES): c1cc2c(ncn3nnc(C4CCCCCC4)c23)[nH]1
InChIKey: QCVMWZJIMQPVCO-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 = 990 nM (pChEMBL 6)
Descriptors: MW 255.32, ALogP 3.04, HBA 4, HBD 1, PSA 58.87, QED 0.68
Compound (SMILES): COc1ccc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2c1Cl
InChIKey: JGMCXSXPMCYLRN-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 348.83, ALogP 3.47, HBA 4, HBD 1, PSA 54.56, QED 0.86
Compound (SMILES): CCS(=N)(=O)Cc1cc(F)cc(Nc2ncc(F)c(-c3ccc(F)cc3OC)n2)c1
InChIKey: OAAHCIALZYFQLH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: CDK9/CycT1 : Recombinant full-length His-tagged human CDK9 and CycT1, expressed in insect cells and purified by Ni-NTA affinity chromatography, were purchase from Invitrogen (Cat. No PV4131). As substrate for the kinase reaction biotinylated peptide biotin-Ttds-YISPLKSPYKISEG (C-terminus in amid form) was used which can be purchased e.g. form the company JERINI peptide technologies (Berlin, Germany) For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 ul of a solution of CDK9/CycT1 in aqueous assay buffer [50 mM Tris/HCl pH 8.0, 10 mM MgCl2, 1.0 mM dithiothreitol, 0.1 mM sodium ortho-vanadate, 0.01% (v/v) Nonidet-P40 (Sigma)] were added and the mixture was incubated for 15 min at 22° C. to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 436.46, ALogP 4.88, HBA 6, HBD 2, PSA 87.96, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C5CCN(C)CC5)c4)nc3c2)c1.Cl
InChIKey: WWJUKYMCFMIUBZ-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 = 1.413 nM (pChEMBL 8.850000381469727)
Descriptors: MW 529.69, ALogP 4.91, HBA 9, HBD 1, PSA 80.57, QED 0.31
Compound (SMILES): CCCS(=O)(=O)Nc1cccc(C(=O)c2c[nH]c3ncc(-c4cnc(OC)nc4)cc23)c1F
InChIKey: QDIMNRNQAKCATG-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 469.5, ALogP 3.55, HBA 7, HBD 2, PSA 126.93, QED 0.38
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C5CCN(S(C)(=O)=O)CC5)c4)nc3c2)c1
InChIKey: IVRYMOBVZPFZQJ-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 = 17.38 nM (pChEMBL 7.760000228881836)
Descriptors: MW 562.7, ALogP 4.66, HBA 9, HBD 0, PSA 102.68, QED 0.29
Compound (SMILES): CCOCc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GOURCRKPQYORGE-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 = 346.74 nM (pChEMBL 6.460000038146973)
Descriptors: MW 443.55, ALogP 5.12, HBA 7, HBD 0, PSA 65.3, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: CESAWDNYOGFNBM-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 = 0.7586 nM (pChEMBL 9.119999885559082)
Descriptors: MW 472.59, ALogP 4.67, HBA 8, HBD 0, PSA 68.54, QED 0.35
Compound (SMILES): Cc1cc(O)cc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c12
InChIKey: RQPCCQZZYVZMOW-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 314.39, ALogP 2.82, HBA 4, HBD 2, PSA 65.56, QED 0.86
Compound (SMILES): [O-][S+](CCN1CCN(CC(O)Cc2ccccc2)CC1)C(c1ccc(F)cc1)c1ccc(F)cc1
InChIKey: MACFTPBZAOCTFN-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at DRD2 (unknown origin) expressed in HEK293T cells transfected with Galphai1-RLuc8 and gamma2-GFP10 assessed as inhibition of quinpirole-induced Gi1 activation pre-incubated with quinpirole for 10 mins before compound incubation for 10 mins by BRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 498.64, ALogP 4.02, HBA 4, HBD 1, PSA 49.77, QED 0.43
Compound (SMILES): BrC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: SUNXMHYYMAXRJE-MGCOHNPYSA-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 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 334.22, ALogP 3.27, HBA 4, HBD 1, PSA 58.87, QED 0.73
Compound (SMILES): CCc1c(-c2cnc3ccc(N(CCNC(C)C)c4cc(OC)cc(OC)c4)cc3n2)cnn1C.Cl
InChIKey: DTLAIVUWXPJAMT-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 = 1.778 nM (pChEMBL 8.75)
Descriptors: MW 474.61, ALogP 4.75, HBA 8, HBD 1, PSA 77.33, QED 0.36
Compound (SMILES): c1ccc2cc(NC3=NC[C@@]4(CN5CCC4CC5)O3)ncc2c1
InChIKey: ZDTPXUKLGIDOCS-SFHVURJKSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P09483
Assay: Agonist activity at rat alpha4beta2 nAChR expressed in HEK293 cells for 2 mins by FLIPR assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 308.39, ALogP 2.5, HBA 5, HBD 1, PSA 49.75, QED 0.88
Compound (SMILES): COC(=O)CCCN/C=C1\C(=O)C(O)=C(C(C)C)c2cc(C)c(-c3c(C)cc4c(c3O)/C(=C/NCCCC(=O)OC)C(=O)C(O)=C4C(C)C)c(O)c21
InChIKey: IHQIQZBZMBBHBD-MFYXSQMNSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of FAM-Bid binding to human MCL1 expressed in Escherichia coli BL21 after 30 mins by fluorescence polarization assay
Measurement: IC50 = 947 nM (pChEMBL 6.019999980926514)
Descriptors: MW 716.83, ALogP 6.16, HBA 12, HBD 6, PSA 191.72, QED 0.08
Compound (SMILES): COc1cc(OC)cc(N(CCNC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YEKLQWUGOHZIQV-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 = 4.677 nM (pChEMBL 8.329999923706055)
Descriptors: MW 444.54, ALogP 3.94, HBA 8, HBD 1, PSA 77.33, QED 0.42
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1cnc2ccccc2c1=O
InChIKey: TVJRDCQUZMGBAB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of partial length human TEC expressed in bacterial system
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 502.57, ALogP 5.32, HBA 5, HBD 3, PSA 114, QED 0.3
Compound (SMILES): [2H]C([2H])([2H])Oc1cc(OC([2H])([2H])[2H])cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C([2H])([2H])C([2H])([2H])NC(C)C)c1
InChIKey: OLAHOMJCDNXHFI-RCEBUFFYSA-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 = 0.4571 nM (pChEMBL 9.34000015258789)
Descriptors: MW 446.56, ALogP 4.18, HBA 8, HBD 1, PSA 77.33, QED 0.41
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN(CCOCCO)CCO1
InChIKey: VDNKDMALAXYLFZ-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 523.42, ALogP 3.78, HBA 9, HBD 2, PSA 98.2, QED 0.36
Compound (SMILES): CNC(=O)c1cc(F)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RFXLZLOSWGJUJY-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 = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 430.49, ALogP 4.08, HBA 6, HBD 1, PSA 75.94, QED 0.5
Compound (SMILES): O=C(c1c(F)ccc(NS(=O)(=O)c2cc(F)ccc2F)c1F)c1c[nH]c2ncc(Cl)cc12
InChIKey: QNOHLXTXYALHSG-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 483.83, ALogP 4.8, HBA 4, HBD 2, PSA 91.92, QED 0.31
Compound (SMILES): COc1cc(F)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: IFLIEMPAHJDKDK-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 = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 446.53, ALogP 4.79, HBA 6, HBD 1, PSA 70.17, QED 0.42
Compound (SMILES): CC1(OC(=O)N2CCC3(CC2)C[C@@H]3CNC(=O)N2Cc3ccncc3C2)COC1
InChIKey: QFORHKAMQGBXQZ-QGZVFWFLSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Reversible inhibition of CYP1A2 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 400.48, ALogP 2.13, HBA 5, HBD 1, PSA 84, QED 0.84