lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1-c1cc(N2CCOCC2)nc(S(C)(=O)=O)n1
InChIKey: BDMRXFODCGLAFM-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: In Vitro Enzyme Assay: Final assay conditions were 4 pM cRaf, 3 uM ATP, 10 nM biotin tagged MEK1 kinase dead protein substrate. Reactions were performed in Greiner384 well plates, catalog #784075. Reaction buffer was 50 mM Tris, pH 7.5, 50 mM NaCl, 10 mM MgCl2, 0.01% Tween-20, 0.05% BSA and 1 mM DTT. 5 ul of 2×cRaf plus MEK1 were dispensed into plates containing 0.25 ul of compound in 100% DMSO and incubated at room temperature for 30 minutes. Reactions were started by addition of 5 ul of 2×ATP. Reactions were run for two hours and terminated by addition of 10 ul of 2× antibody and Alphascreen bead mixture in Stop Buffer. Stop Buffer was 50 mM Tris, pH 7.5, 0.005% Tween-20, 25 mM EDTA.
Measurement: IC50 = 0.11 nM (pChEMBL 9.960000038146973)
Descriptors: MW 520.53, ALogP 3.96, HBA 7, HBD 1, PSA 101.49, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCNS(=O)(=O)N(C)C)c4)nc3c2)c1
InChIKey: JCBRKJGZGWDDLQ-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 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 551.67, ALogP 3.45, HBA 9, HBD 1, PSA 114.71, QED 0.28
Compound (SMILES): COc1cc(C(=O)N2CCCC2)cc(N(CCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: XIGQDVFIOYNOFH-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 = 223.87 nM (pChEMBL 6.650000095367432)
Descriptors: MW 486.58, ALogP 3.8, HBA 8, HBD 1, PSA 96.61, QED 0.4
Compound (SMILES): CCN(CC)C(=O)c1cc(-c2cccs2)nc2c1c(C)nn2-c1ccccc1C
InChIKey: SFKDMBHAUPXODT-UHFFFAOYSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: In Vitro Enzyme Assay: In vitro enzyme assays were conducted via the Ba(OH)2 precipitation method of Wang et al. (32) using recombinant human PDE11A4, PDE10A1, PDE5A1, PDE6C, PDE8A (BPS Bioscience Inc.), PDE7A (BIOMOL International), and PDE4A10 enzymes (gift from HengmingKe), in the presence of 100 nM cGMP, 30 nM cAMP, 500 nM cGMP, 1.7 μM cGMP, 10 nM cAMP, 15 nM cAMP, and 625 nM cAMP, respectively. Inhibitor concentrations that reduce enzyme activity by 50% (IC50) are presented. The values are means of at least three independent experiments.
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 404.54, ALogP 5.25, HBA 5, HBD 0, PSA 51.02, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QEOQAZAFSABGFK-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 = 288.4 nM (pChEMBL 6.539999961853027)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): Cc1cc(OC(F)F)cnc1C(=O)Nc1csc([C@]23CO[C@@H](C)C[C@H]2CSC(N)=N3)n1
InChIKey: CHAGAOAUIITKPC-ADWYPQAOSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Displacement of [3H]-PF-6475886 from recombinant human full length Myc-DDK-tagged BACE2 expressed in HEK293 cell membranes after 30 mins by parallel scintillation proximity assay
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 469.54, ALogP 3.38, HBA 9, HBD 2, PSA 111.72, QED 0.69
Compound (SMILES): N#Cc1cc(F)c(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)c(F)c1
InChIKey: CJNMJHYWMBVVBL-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 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 393.4, ALogP 3.14, HBA 6, HBD 1, PSA 85.9, QED 0.58
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(OC)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KIDZNCKPIJZGHH-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 = 4.266 nM (pChEMBL 8.369999885559082)
Descriptors: MW 516.65, ALogP 4.69, HBA 9, HBD 0, PSA 77.77, QED 0.3
Compound (SMILES): COc1cc(Cl)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HYIAWTNBECBRDG-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 = 102.33 nM (pChEMBL 6.989999771118164)
Descriptors: MW 419.92, ALogP 5.24, HBA 6, HBD 0, PSA 56.07, QED 0.43
Compound (SMILES): O=C(CCc1ccc(F)cc1CN1CCC[C@H]1c1nc(C(=O)NCCCCC2CCCCC2)co1)NS(=O)(=O)C(F)(F)F
InChIKey: BJUUQOLZOPQZKM-VWLOTQADSA-N
Target: Thromboxane A2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21731
Assay: Cell Based Assay: Ca2+ signaling studies were performed using a FLIPR TETRA system (Molecular Devices, Sunnyvale, Calif., USA) in the 384-format. This is a high-throughput instrument for cell-based assays to monitor Ca2+ signaling associated with GPCRs and ion channels. Cells were seeded at a density of 5×104 cells/well in BioCoat poly-D-lysine coated, black wall, clear bottom 384-well plates (BD Biosciences, Franklin lakes, NJ, USA) and allowed to attach overnight in an incubator at 37° C. The cells were then washed twice with HBSS-HEPES buffer (Hanks' balanced salt solution without bicarbonate and phenol red, 20 mM HEPES, pH 7.4) using an ELx405 Select CW Microplate Washer (BioTek, Winooski, Vt., USA). After 60 min of dye-loading in the dark using the Ca2+-sensitive dye Fluo-4AM (Invitrogen, Carlsbad, Calif., USA), at a final concentration of 2×10^−6M, the plates were washed 4 times with HBSS-HEPES buffer to remove excess dye and leaving 50 μl of buffer in each well. The plates were then placed in the FLIPR TETRA instrument and allowed to equilibrate at 37° C. AGN-211377 was added in a 25 μl volume to each well to give final concentrations of 0.1 μM, 0.3 μM, 1 μM, 3 μM, 10 μM, and 30 μM; or 0.067 μM, 0.1 μM, 0.2 μM, 0.3 μM, 0.67 μM, and 1 μM for cells over-expressing TP receptors. After 4.5 minutes, a 7-point serial dilution of the standard agonist for the corresponding receptor, in a 25 μl volume was injected at the final concentrations from 10^−11M to 10^−5M in 10-fold serial dilution increments for cells expressing human recombinant DP1, EP1, EP2, EP3, EP4, FP, and IP receptors. The dose range for the standard agonist for human recombinant TP receptors was from 10^−12M to 10^−6M. HBSS-HEPES buffer was used as the negative control for the standard agonists. Cells were excited with LED (light emitting diode) excitation at 470-495 nm and emission was measured through an emission filter at 515-575 nm. Assay plates were read for 3.5 minutes using the FLIPRTETRA.
Measurement: EC50 < 1 nM (pChEMBL 9)
Descriptors: MW 630.7, ALogP 5.53, HBA 7, HBD 2, PSA 121.61, QED 0.22
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCN(C(=O)C3CC3)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BSINISOJOVJBAT-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 = 7.762 nM (pChEMBL 8.109999656677246)
Descriptors: MW 541.66, ALogP 3.74, HBA 9, HBD 0, PSA 88.85, QED 0.32
Compound (SMILES): CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2OC)CCC[C@@H](N2CCN(CCO)CC2)C3)ncc1Cl
InChIKey: BCSHRERPHLTPEE-OAQYLSRUSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate in presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 5600 nM (pChEMBL 5.251999855041504)
Descriptors: MW 580.13, ALogP 3.84, HBA 9, HBD 4, PSA 114.88, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CCn2nccc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PODHQRDKTIXYRI-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 = 69.18 nM (pChEMBL 7.159999847412109)
Descriptors: MW 469.55, ALogP 4.39, HBA 9, HBD 0, PSA 83.12, QED 0.33
Compound (SMILES): Cn1cc(-c2ccc3ncc(N(CCN)c4cc(F)cc(OCCO)c4)nc3c2)cn1
InChIKey: HIMWRONMJKQVOO-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 = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 422.46, ALogP 2.64, HBA 8, HBD 2, PSA 102.32, QED 0.45
Compound (SMILES): CCO[C@@H]1C[C@H](C(=O)Nc2ccc(N3CCOCC3=O)cc2)N(C(=O)Nc2ccc(Cl)cc2)C1
InChIKey: MWCQXJXNQGSKRK-NHCUHLMSSA-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. 30 min pre-incubation of enzyme with compound and 60 min reaction time after substrate addition.
Measurement: IC50 = 0.737 nM (pChEMBL 9.130000114440918)
Descriptors: MW 486.96, ALogP 3.35, HBA 5, HBD 2, PSA 100.21, QED 0.65
Compound (SMILES): CC(C)(Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: FJEJHTFPLBTMLO-SFHVURJKSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: In Vitro Fluorescence Assay: A continuous assay is used in which the substrate is a synthetic peptide containing a fluorescent group (7-methoxycoumarin, Mca), which is quenched by energy transfer to a 2,4-dinitrophenyl group. The substrate is the peptide Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH. When the peptide is cleaved by MMP a large increase in fluorescence is observed. The source of the enzyme for this assay is full-length, recombinant, human pro-MMP-2 expressed in Chinese Hamster Ovary (CHO) cells that is subsequently activated by an organomercurial compound, 4-aminophenyl mercuric acetate (APMA). APMA is removed through a desalting column (MMP-2 Calbiochem catalog number PF023). The assay buffer consists of 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2 and 10 uM human serum albumin Each well of the 96-well plates consists of a 100 uL reaction mixture consisting of assay buffer, MMP (final concentration of 0.2 nM, prepared by diluting in assay buffer).
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 397.4, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.64
Compound (SMILES): CC(C)N1CCC(NC(=O)c2nn(Cc3cc(-c4ccc(Cl)s4)on3)c3ccc(C(=O)NC#N)cc23)CC1
InChIKey: GPRXTQVZUIPWGU-UHFFFAOYSA-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. 30 min pre-incubation of enzyme with compound and 60 min reaction time after substrate addition.
Measurement: IC50 = 8.78 nM (pChEMBL 8.0600004196167)
Descriptors: MW 552.06, ALogP 4.27, HBA 9, HBD 2, PSA 129.08, QED 0.26
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCN4CCCC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: VZUAVFLTRIZLOD-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 = 2.884 nM (pChEMBL 8.539999961853027)
Descriptors: MW 529.65, ALogP 3.88, HBA 9, HBD 1, PSA 97.64, QED 0.31
Compound (SMILES): COC[C@H](CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1)OC(C)=O
InChIKey: BFLRXUQCNYUNBN-QHCPKHFHSA-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 = 47.86 nM (pChEMBL 7.320000171661377)
Descriptors: MW 491.55, ALogP 3.76, HBA 10, HBD 0, PSA 100.83, QED 0.31
Compound (SMILES): COc1cc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2cc1C
InChIKey: XBUXVLRXGOHFLE-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
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 328.41, ALogP 3.13, HBA 4, HBD 1, PSA 54.56, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCNCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YXFOOAQCZMCCOW-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 = 4.365 nM (pChEMBL 8.359999656677246)
Descriptors: MW 487.61, ALogP 3.48, HBA 9, HBD 1, PSA 80.57, QED 0.38
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCC2=O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YEGXHZZEFKJQGY-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 = 2.884 nM (pChEMBL 8.539999961853027)
Descriptors: MW 486.58, ALogP 4.2, HBA 8, HBD 0, PSA 85.61, QED 0.35
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4ccc(Oc5ccccc5)cc4)nn32)CC1
InChIKey: RNOAOAWBMHREKO-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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 471.56, ALogP 4.22, HBA 6, HBD 2, PSA 102.48, QED 0.52
Compound (SMILES): FC(F)(F)Oc1ccc(NC[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: BPPYAKNDAZSIQO-HDJSIYSDSA-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 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 430.43, ALogP 4.89, HBA 6, HBD 2, PSA 80.13, QED 0.47
Compound (SMILES): CNC(=O)OCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: USWTXIMYBIOVHO-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 = 6.761 nM (pChEMBL 8.170000076293945)
Descriptors: MW 462.51, ALogP 3.54, HBA 9, HBD 1, PSA 103.63, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCCC(C#N)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HXQAPCVVLVJETP-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 nM (pChEMBL 8)
Descriptors: MW 497.6, ALogP 4.42, HBA 9, HBD 0, PSA 92.33, QED 0.35
Compound (SMILES): CC(C)Oc1cc(NC(=O)N2CCCc3ccc(C=O)nc32)ncc1C#N
InChIKey: KYVKVDHCJPYHLM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: Q03142
Assay: Inhibition of FGFR4 in mouse BAF3 cells assessed as decrease in FGFR4 phosphorylation incubated for 40 mins
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 365.39, ALogP 2.93, HBA 6, HBD 1, PSA 108.21, QED 0.83
Compound (SMILES): CC(=O)c1ccc(C(=O)O)c(Nc2ccccc2C(=O)O)c1
InChIKey: VNDSZOSZZSPPFX-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Discontinuous Radiometric Assay: Compounds may be evaluated as selective reversible inhibitors of AKR1C3 by screening them against homogeneous recombinant AKR1C1-AKR1C4 expressed in E. coli. In each case, a discontinuous radiometric assay may be used to monitor the inhibition of progesterone reduction (20-ketosteroid reduction) catalyzed by AKR1C1, the inhibition of Δ4-AD reduction (17-ketosteroid reduction) catalyzed by AKR1C3, and the inhibition of 5α-DHT reduction (3-ketosteroid reduction) catalyzed by AKR1C2 and AKR1C4 (by measuring the formation of 20α-hydroxyprogesterone, testosterone or 3α-androstanediol by radiochromatography). Secondary screens of the compounds of interest include: (a) a full-screen against all nine human recombinant AKR enzymes to ensure there are no-intended off-target effects (in this context AKR1B10 (retinal reductase; SEQ ID NO:5) has been shown to be potently inhibited by N-phenylanthranilates) (Endo et al., 2010, Biol. Pharm. Bull. 33:886-90); (b) a screen against COX-1 and COX-2 to reaffirm that compounds do not act as NSAIDs; and (c) an expanded screen against other nuclear receptors (especially other steroid hormone receptors).
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 299.28, ALogP 3.03, HBA 4, HBD 3, PSA 103.7, QED 0.73
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)s2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: CKZSTRXMCOYTCV-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 = 165.96 nM (pChEMBL 6.78000020980835)
Descriptors: MW 477.98, ALogP 6.09, HBA 7, HBD 1, PSA 76.16, QED 0.31
Compound (SMILES): COCCOc1cc(NC(=O)N2CCCc3cc(CN4CCN(C)CC4=O)c(C=O)nc32)ncc1C#N
InChIKey: LGFNXKJQQVMYQI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 kinase domain (406 to 821) (unknown origin) using 5-FluoAhx-EEPLYWSFPAKKKCO-NH2 peptide as substrate in presence of ATP measured after 60 mins by caliper microfluidic mobility shift assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 507.55, ALogP 1.44, HBA 9, HBD 1, PSA 140.99, QED 0.41
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCCNCCS(C)(=O)=O)c4)nc3c2)c1
InChIKey: RUEUJHIYTXZELK-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 564.71, ALogP 4.08, HBA 10, HBD 1, PSA 111.47, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(CCO)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NVJBAXNECMDGLO-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 = 2.884 nM (pChEMBL 8.539999961853027)
Descriptors: MW 516.65, ALogP 4.28, HBA 9, HBD 1, PSA 88.77, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CC2CCN(C(C)C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: URQOCFMHKKPXJG-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 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 500.65, ALogP 5.31, HBA 8, HBD 0, PSA 68.54, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccccc2C#N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: UYAYNOCUUTUNCS-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 = 269.15 nM (pChEMBL 6.570000171661377)
Descriptors: MW 500.56, ALogP 5.11, HBA 8, HBD 0, PSA 89.09, QED 0.3
Compound (SMILES): COc1cc(F)cc(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: NQBHHGUWHWBUDK-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 = 2.089 nM (pChEMBL 8.680000305175781)
Descriptors: MW 420.49, ALogP 4.3, HBA 6, HBD 2, PSA 78.96, QED 0.44
Compound (SMILES): O=C(c1c(F)ccc(NS(=O)(=O)c2c(F)cccc2F)c1F)c1c[nH]c2ncc(Cl)cc12
InChIKey: WFFKYXSMOWEGGR-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 483.83, ALogP 4.8, HBA 4, HBD 2, PSA 91.92, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(Cc2cccc(N(C)C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ZRDNUCXRIXLMNC-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 = 61.66 nM (pChEMBL 7.210000038146973)
Descriptors: MW 495.59, ALogP 4.85, HBA 9, HBD 0, PSA 81.43, QED 0.3
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1-c1cc(N2CCOCC2)nc(S(C)(=O)=O)n1
InChIKey: BDMRXFODCGLAFM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Raf Activity Assay: Raf and biotinylated Mek, kinase dead, were combined at 2x final concentrations in assay buffer (50 mM Tris, pH 7.5, 15 mM MgCl2, 0.01% BSA and 1 mM DTT) and dispensed 5 ml per well in assay plates (Greiner white 384 well assay plates #781207) containing 0.25 ml of 40x of a Raf kinase inhibitor test compound diluted in 100% DMSO. The plate was incubated for 60 minutes at room temperature. The Raf kinase activity reaction was started by the addition of 5 mL per well of 2xATP diluted in assay buffer. After 3 hours (b-Raf(V600E)) or 1 hour (c-Raf). The reactions were stopped and the phosphorylated product was measured using a rabbit anti-p-MEK (Cell Signaling, #9121) antibody and the Alpha Screen IgG (ProteinA) detection Kit (PerkinElmer #6760617R), by the addition of 10 mL to the well of a mixture of the antibody (1:2000 dilution) and detection beads (1:2000 dilution of both beads) in Stop/bead buffer (25 mM EDTA, 50 mM Tris, pH 7.5, 0.01% Tween20). The additions were carried out under dark conditions to protect the detection beads from light. A lid was placed on top of the plate and incubated for 1 hour at room temperature, then the luminescence was read on a PerkinElmer Envision instrument. The concentration of each compound for 50% inhibition (IC50) was calculated by non-linear regression using XL Fit data analysis software.
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 520.53, ALogP 3.96, HBA 7, HBD 1, PSA 101.49, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCNS(=O)(=O)N(C)C)c4)nc3c2)c1
InChIKey: JCBRKJGZGWDDLQ-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 = 10 nM (pChEMBL 8)
Descriptors: MW 551.67, ALogP 3.45, HBA 9, HBD 1, PSA 114.71, QED 0.28
Compound (SMILES): COc1cc(C(=O)N2CCCC2)cc(N(CCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: XIGQDVFIOYNOFH-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 = 208.93 nM (pChEMBL 6.679999828338623)
Descriptors: MW 486.58, ALogP 3.8, HBA 8, HBD 1, PSA 96.61, QED 0.4
Compound (SMILES): CCN(CC)C(=O)c1cc(-c2cccs2)nc2c1c(C)nn2-c1ccccc1C
InChIKey: SFKDMBHAUPXODT-UHFFFAOYSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: In Vitro Enzyme Assay: In vitro enzyme assays were conducted via the Ba(OH)2 precipitation method of Wang et al. (32) using recombinant human PDE11A4, PDE10A1, PDE5A1, PDE6C, PDE8A (BPS Bioscience Inc.), PDE7A (BIOMOL International), and PDE4A10 enzymes (gift from HengmingKe), in the presence of 100 nM cGMP, 30 nM cAMP, 500 nM cGMP, 1.7 μM cGMP, 10 nM cAMP, 15 nM cAMP, and 625 nM cAMP, respectively. Inhibitor concentrations that reduce enzyme activity by 50% (IC50) are presented. The values are means of at least three independent experiments.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 404.54, ALogP 5.25, HBA 5, HBD 0, PSA 51.02, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QEOQAZAFSABGFK-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 = 218.78 nM (pChEMBL 6.659999847412109)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(OC)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KIDZNCKPIJZGHH-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 = 4.169 nM (pChEMBL 8.380000114440918)
Descriptors: MW 516.65, ALogP 4.69, HBA 9, HBD 0, PSA 77.77, QED 0.3
Compound (SMILES): COc1cc(Cl)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HYIAWTNBECBRDG-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 = 44.67 nM (pChEMBL 7.349999904632568)
Descriptors: MW 419.92, ALogP 5.24, HBA 6, HBD 0, PSA 56.07, QED 0.43
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCN(C(=O)C3CC3)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BSINISOJOVJBAT-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 = 19.5 nM (pChEMBL 7.710000038146973)
Descriptors: MW 541.66, ALogP 3.74, HBA 9, HBD 0, PSA 88.85, QED 0.32
Compound (SMILES): CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2OC)CCC[C@@H](N2CCN(CCO)CC2)C3)ncc1Cl
InChIKey: BCSHRERPHLTPEE-OAQYLSRUSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate in presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 5600 nM (pChEMBL 5.251999855041504)
Descriptors: MW 580.13, ALogP 3.84, HBA 9, HBD 4, PSA 114.88, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CCn2nccc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PODHQRDKTIXYRI-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 = 32.36 nM (pChEMBL 7.489999771118164)
Descriptors: MW 469.55, ALogP 4.39, HBA 9, HBD 0, PSA 83.12, QED 0.33
Compound (SMILES): Cn1cc(-c2ccc3ncc(N(CCN)c4cc(F)cc(OCCO)c4)nc3c2)cn1
InChIKey: HIMWRONMJKQVOO-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 = 10.23 nM (pChEMBL 7.989999771118164)
Descriptors: MW 422.46, ALogP 2.64, HBA 8, HBD 2, PSA 102.32, QED 0.45
Compound (SMILES): CCO[C@@H]1C[C@H](C(=O)Nc2ccc(N3CCOCC3=O)cc2)N(C(=O)Nc2ccc(Cl)cc2)C1
InChIKey: MWCQXJXNQGSKRK-NHCUHLMSSA-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. 60 min pre-incubation of enzyme with compound and 15 min reaction time after substrate addition.
Measurement: IC50 = 0.624 nM (pChEMBL 9.210000038146973)
Descriptors: MW 486.96, ALogP 3.35, HBA 5, HBD 2, PSA 100.21, QED 0.65
Compound (SMILES): CC(C)(Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: FJEJHTFPLBTMLO-SFHVURJKSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: In Vitro Fluorescence Assay: A continuous assay is used in which the substrate is a synthetic peptide containing a fluorescent group (7-methoxycoumarin, Mca), which is quenched by energy transfer to a 2,4-dinitrophenyl group. The substrate is the peptide Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH. When the peptide is cleaved by MMP a large increase in fluorescence is observed. The source of the enzyme for this assay is full-length, recombinant, human pro-MMP-2 expressed in Chinese Hamster Ovary (CHO) cells that is subsequently activated by an organomercurial compound, 4-aminophenyl mercuric acetate (APMA). APMA is removed through a desalting column (MMP-2 Calbiochem catalog number PF023). The assay buffer consists of 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2 and 10 uM human serum albumin Each well of the 96-well plates consists of a 100 uL reaction mixture consisting of assay buffer, MMP (final concentration of 0.2 nM, prepared by diluting in assay buffer).
Measurement: IC50 = 7590 nM (pChEMBL 5.119999885559082)
Descriptors: MW 397.4, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.64
Compound (SMILES): CC(C)N1CCC(NC(=O)c2nn(Cc3cc(-c4ccc(Cl)s4)on3)c3ccc(C(=O)NC#N)cc23)CC1
InChIKey: GPRXTQVZUIPWGU-UHFFFAOYSA-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. 60 min pre-incubation of enzyme with compound and 15 min reaction time after substrate addition.
Measurement: IC50 = 6.71 nM (pChEMBL 8.170000076293945)
Descriptors: MW 552.06, ALogP 4.27, HBA 9, HBD 2, PSA 129.08, QED 0.26
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCN4CCCC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: VZUAVFLTRIZLOD-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 = 2.291 nM (pChEMBL 8.640000343322754)
Descriptors: MW 529.65, ALogP 3.88, HBA 9, HBD 1, PSA 97.64, QED 0.31
Compound (SMILES): COC[C@H](CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1)OC(C)=O
InChIKey: BFLRXUQCNYUNBN-QHCPKHFHSA-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 = 34.67 nM (pChEMBL 7.460000038146973)
Descriptors: MW 491.55, ALogP 3.76, HBA 10, HBD 0, PSA 100.83, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCNCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YXFOOAQCZMCCOW-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 = 5.129 nM (pChEMBL 8.289999961853027)
Descriptors: MW 487.61, ALogP 3.48, HBA 9, HBD 1, PSA 80.57, QED 0.38
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCC2=O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YEGXHZZEFKJQGY-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 = 3.715 nM (pChEMBL 8.430000305175781)
Descriptors: MW 486.58, ALogP 4.2, HBA 8, HBD 0, PSA 85.61, QED 0.35
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4ccc(Oc5ccccc5)cc4)nn32)CC1
InChIKey: RNOAOAWBMHREKO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 0.63 nM (pChEMBL 9.199999809265137)
Descriptors: MW 471.56, ALogP 4.22, HBA 6, HBD 2, PSA 102.48, QED 0.52
Compound (SMILES): CNC(=O)OCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: USWTXIMYBIOVHO-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 = 2.692 nM (pChEMBL 8.569999694824219)
Descriptors: MW 462.51, ALogP 3.54, HBA 9, HBD 1, PSA 103.63, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCCC(C#N)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HXQAPCVVLVJETP-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 = 4.786 nM (pChEMBL 8.319999694824219)
Descriptors: MW 497.6, ALogP 4.42, HBA 9, HBD 0, PSA 92.33, QED 0.35
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)s2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: CKZSTRXMCOYTCV-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 = 144.54 nM (pChEMBL 6.840000152587891)
Descriptors: MW 477.98, ALogP 6.09, HBA 7, HBD 1, PSA 76.16, QED 0.31
Compound (SMILES): COCCOc1cc(NC(=O)N2CCCc3cc(CN4CCN(C)CC4=O)c(C=O)nc32)ncc1C#N
InChIKey: LGFNXKJQQVMYQI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 kinase domain (407 to 822) (unknown origin) using 5-FluoAhx-EEPLYWSFPAKKKCO-NH2 peptide as substrate in presence of ATP measured after 60 mins by caliper microfluidic mobility shift assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 507.55, ALogP 1.44, HBA 9, HBD 1, PSA 140.99, QED 0.41
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCCNCCS(C)(=O)=O)c4)nc3c2)c1
InChIKey: RUEUJHIYTXZELK-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 = 3.548 nM (pChEMBL 8.449999809265137)
Descriptors: MW 564.71, ALogP 4.08, HBA 10, HBD 1, PSA 111.47, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(CCO)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NVJBAXNECMDGLO-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 = 4.074 nM (pChEMBL 8.390000343322754)
Descriptors: MW 516.65, ALogP 4.28, HBA 9, HBD 1, PSA 88.77, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CC2CCN(C(C)C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: URQOCFMHKKPXJG-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 = 30.9 nM (pChEMBL 7.510000228881836)
Descriptors: MW 500.65, ALogP 5.31, HBA 8, HBD 0, PSA 68.54, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccccc2C#N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: UYAYNOCUUTUNCS-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 = 275.42 nM (pChEMBL 6.559999942779541)
Descriptors: MW 500.56, ALogP 5.11, HBA 8, HBD 0, PSA 89.09, QED 0.3
Compound (SMILES): COc1cc(F)cc(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: NQBHHGUWHWBUDK-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 = 3.236 nM (pChEMBL 8.489999771118164)
Descriptors: MW 420.49, ALogP 4.3, HBA 6, HBD 2, PSA 78.96, QED 0.44
Compound (SMILES): COc1cc(OC)cc(N(Cc2cccc(N(C)C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ZRDNUCXRIXLMNC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 380.19 nM (pChEMBL 6.420000076293945)
Descriptors: MW 495.59, ALogP 4.85, HBA 9, HBD 0, PSA 81.43, QED 0.3
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1-c1cc(N2CCOCC2)nc(S(C)(=O)=O)n1
InChIKey: BDMRXFODCGLAFM-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: In Vitro Raf Activity: Raf and biotinylated Mek, kinase dead, were combined at 2× final concentrations in assay buffer (50 mM Tris, pH 7.5, 15 mM MgCl2, 0.01% BSA and 1 mM DTT) and dispensed 5 ml per well in assay plates (Greiner white 384 well assay plates #781207) containing 0.25 ml of 40× of a Raf kinase inhibitor test compound diluted in 100% DMSO. The plate was incubated for 60 minutes at room temperature. The Raf kinase activity reaction was started by the addition of 5 mL per well of 2×ATP diluted in assay buffer. After 3 hours (b-Raf(V600E)) or 1 hour (c-Raf). The reactions were stopped and the phosphorylated product was measured using a rabbit anti-p-MEK (Cell Signaling, #9121) antibody and the Alpha Screen IgG (ProteinA) detection Kit (PerkinElmer #6760617R), by the addition of 10 mL to the well of a mixture of the antibody (1:2000 dilution) and detection beads (1:2000 dilution of both beads) in Stop/bead buffer (25 mM EDTA, 50 mM Tris, pH 7.5, 0.01% Tween20). The additions were carried out under dark conditions to protect the detection beads from light. A lid was placed on top of the plate and incubated for 1 hour at room temperature, then the luminescence was read on a PerkinElmer Envision instrument. The concentration of each compound for 50% inhibition (IC50) was calculated by non-linear regression using XL Fit data analysis software.
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 520.53, ALogP 3.96, HBA 7, HBD 1, PSA 101.49, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCNS(=O)(=O)N(C)C)c4)nc3c2)c1
InChIKey: JCBRKJGZGWDDLQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 37.15 nM (pChEMBL 7.429999828338623)
Descriptors: MW 551.67, ALogP 3.45, HBA 9, HBD 1, PSA 114.71, QED 0.28
Compound (SMILES): COc1cc(C(=O)N2CCCC2)cc(N(CCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: XIGQDVFIOYNOFH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 486.58, ALogP 3.8, HBA 8, HBD 1, PSA 96.61, QED 0.4
Compound (SMILES): CCN(CC)C(=O)c1cc(-c2cccs2)nc2c1c(C)nn2-c1ccccc1C
InChIKey: SFKDMBHAUPXODT-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: In Vitro Enzyme Assay: In vitro enzyme assays were conducted via the Ba(OH)2 precipitation method of Wang et al. (32) using recombinant human PDE11A4, PDE10A1, PDE5A1, PDE6C, PDE8A (BPS Bioscience Inc.), PDE7A (BIOMOL International), and PDE4A10 enzymes (gift from HengmingKe), in the presence of 100 nM cGMP, 30 nM cAMP, 500 nM cGMP, 1.7 μM cGMP, 10 nM cAMP, 15 nM cAMP, and 625 nM cAMP, respectively. Inhibitor concentrations that reduce enzyme activity by 50% (IC50) are presented. The values are means of at least three independent experiments.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 404.54, ALogP 5.25, HBA 5, HBD 0, PSA 51.02, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QEOQAZAFSABGFK-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 660.69 nM (pChEMBL 6.179999828338623)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): Cc1cc(OC(F)F)cnc1C(=O)Nc1csc([C@]23CO[C@@H](C)C[C@H]2CSC(N)=N3)n1
InChIKey: CHAGAOAUIITKPC-ADWYPQAOSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: CYP2D6 inhibition was obtained by measuring inhibition of 5 uM Dextromethorphan in pooled HLM (HL-MIX-102).
Measurement: IC50 < 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 469.54, ALogP 3.38, HBA 9, HBD 2, PSA 111.72, QED 0.69
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(OC)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KIDZNCKPIJZGHH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 516.65, ALogP 4.69, HBA 9, HBD 0, PSA 77.77, QED 0.3
Compound (SMILES): COc1cc(Cl)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HYIAWTNBECBRDG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 419.92, ALogP 5.24, HBA 6, HBD 0, PSA 56.07, QED 0.43
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCN(C(=O)C3CC3)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BSINISOJOVJBAT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 83.18 nM (pChEMBL 7.079999923706055)
Descriptors: MW 541.66, ALogP 3.74, HBA 9, HBD 0, PSA 88.85, QED 0.32
Compound (SMILES): CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2OC)CCC[C@@H](N2CCN(CCO)CC2)C3)ncc1Cl
InChIKey: BCSHRERPHLTPEE-OAQYLSRUSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone/midazolam as substrate in presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 5600 nM (pChEMBL 5.251999855041504)
Descriptors: MW 580.13, ALogP 3.84, HBA 9, HBD 4, PSA 114.88, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CCn2nccc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PODHQRDKTIXYRI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 229.09 nM (pChEMBL 6.639999866485596)
Descriptors: MW 469.55, ALogP 4.39, HBA 9, HBD 0, PSA 83.12, QED 0.33
Compound (SMILES): Cn1cc(-c2ccc3ncc(N(CCN)c4cc(F)cc(OCCO)c4)nc3c2)cn1
InChIKey: HIMWRONMJKQVOO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 30.9 nM (pChEMBL 7.510000228881836)
Descriptors: MW 422.46, ALogP 2.64, HBA 8, HBD 2, PSA 102.32, QED 0.45