lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ncc(F)cc1[C@H]1CCCN1c1ccn2ncc(C(=O)NC3CCC(O)CC3)c2n1
InChIKey: WRXZQYJJPXFOIB-LADRWXRNSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Tyk2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 8 μM Omnia Y12 peptide (Catalog # IVGN KPZ3121C; Invitrogen Corporation, Carlsbad, Calif.) and 1 nM Tyk2 in a total volume of 20 μL. Human Tyk2 kinase domain, comprising amino acids 886 to 1187 with 10 additional histidine residues (histidine tag) on the carboxy terminus, was expressed and purified from bacculovirus in-house at Array BioPharma Inc. (Boulder, Colo.). The histidine tag was cleaved after purification using standard conditions.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 454.51, ALogP 2.65, HBA 8, HBD 2, PSA 104.88, QED 0.61
Compound (SMILES): COc1ncc(-c2cnc3[nH]cc(C(=O)c4c(F)ccc(NS(=O)(=O)c5cc(F)ccc5F)c4F)c3c2)cn1
InChIKey: HNZHVLFQWSISBO-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using AMMC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 557.49, ALogP 4.62, HBA 7, HBD 2, PSA 126.93, QED 0.22
Compound (SMILES): COc1ccc(CCC(=O)NS(=O)(=O)C(F)(F)F)c(CN2CCC[C@H]2c2nc(C(=O)NCCCCC3CCCCC3)co2)c1
InChIKey: ZBYCYKAOQOIIRO-SANMLTNESA-N
Target: Prostacyclin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43119
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 = 9500 nM (pChEMBL 5.019999980926514)
Descriptors: MW 642.74, ALogP 5.4, HBA 8, HBD 2, PSA 130.84, QED 0.26
Compound (SMILES): C[C@H]1Cc2c(nnn2-c2ncc(F)cn2)CN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: HSWKCWMWNVSZGG-VIFPVBQESA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-Mephenytoin as substrate
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 440.79, ALogP 3.46, HBA 6, HBD 0, PSA 76.8, QED 0.57
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCCN1CCCC1
InChIKey: INTICWGTKLQPSH-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 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 433.34, ALogP 5.16, HBA 6, HBD 1, PSA 59.51, QED 0.56
Compound (SMILES): COc1cccc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XKYKMEFXVHYFRM-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 = 38.02 nM (pChEMBL 7.420000076293945)
Descriptors: MW 375.43, ALogP 3.17, HBA 7, HBD 1, PSA 76.3, QED 0.56
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCN(C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WZWCHRIODAFYKY-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 = 3.631 nM (pChEMBL 8.4399995803833)
Descriptors: MW 487.61, ALogP 3.43, HBA 9, HBD 0, PSA 71.78, QED 0.37
Compound (SMILES): CCOc1nc2ccc(C(O)(c3ccc(C(F)(F)F)nc3)c3cncn3C)cc2c(C(F)(F)F)c1Oc1ccc(Cl)cc1
InChIKey: DJTRYZOLOWBFQI-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: RORγt Reporter Assay: The reporter assay was performed by transiently transfecting HEK293T cells with 5 μg of pBIND-RORγt LBD or pBIND-RORγt LBD-AF2 and 5 μg pGL4.31 (Promega Cat no. C935A) using Fugene 6 (Invitrogen Cat no. E2691) at a 1:6 ratio of DNA: Fugene 6 in a T-75 flask in which cells were at least 80% confluent. Twenty four hours after bulk transfection, cells were plated into 96-well plates at 50,000 cells/well in phenol-red free DMEM containing 5% Lipid Reduced FCS and Pen/Strep. Six hours after plating, cells were treated with compounds for 24 hours. Media was removed and cells were lysed with 50 μL 1x Glo Lysis Buffer (Promega). Dual Glo Luciferase Reagent (50 μL/well) was then added and firefly luciferase luminescence was read on an Envision after a ten minute incubation. Finally, Stop and Glo reagent (50 μL/well) was added and renilla luciferase luminescence was read on an Envision after a ten minute incubation.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 622.95, ALogP 7.53, HBA 7, HBD 1, PSA 82.29, QED 0.19
Compound (SMILES): COc1cc(OC)cc(N(CCc2nnn[nH]2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YMXQQOATOHFDLF-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 = 4.074 nM (pChEMBL 8.390000343322754)
Descriptors: MW 457.5, ALogP 2.94, HBA 10, HBD 1, PSA 119.76, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H](O)C(F)(F)F)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: JXGGHGLZZYBWNG-XMMPIXPASA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.188 nM (pChEMBL 8.65999984741211)
Descriptors: MW 501.51, ALogP 5.15, HBA 8, HBD 1, PSA 85.53, QED 0.36
Compound (SMILES): CCC(=O)N1CC[C@H](Oc2ccnc3ccc(-c4ccc(OC)nc4)cc23)C1
InChIKey: GKVUBNGBTYQPGF-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3K-gamma (unknown origin) by KinaseGlo assay
Measurement: IC50 = 828 nM (pChEMBL 6.079999923706055)
Descriptors: MW 377.44, ALogP 3.7, HBA 5, HBD 0, PSA 64.55, QED 0.68
Compound (SMILES): CN[C@@H](C)C(=O)Nc1ccc(-c2c(-c3cncn3C)nc3cc(C)ccn23)c(C#Cc2ccc3c(C)nccc3c2)n1
InChIKey: MKBRPDBPQLDLIT-QFIPXVFZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assays: The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), a certain concentration of human liver microsomes dependent on the P450 isoenzyme measured (P450 2C9, P450 3A4: 0.1 mg/ml; P450 2D6: 0.2 mg/ml; P450 2C19: 0.5 mg/ml; P450 2C8: 0.05 mg/ml) and a certain concentration of the individual substrate for each isoenzyme (P450 2C9: Diclofenac 10 μM; P450 3A4: Midazolam 5 μM; P450 2D6: Dextromethorphan 5 μM; P450 2C19: S-Mephenytoin 70 μM; P450 2C8: Amodiaquine 1 μM).
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 554.66, ALogP 4.91, HBA 8, HBD 2, PSA 102.03, QED 0.29
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCCC2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: SIWFRERSMYFRNO-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 = 1.148 nM (pChEMBL 8.9399995803833)
Descriptors: MW 500.65, ALogP 5.45, HBA 8, HBD 0, PSA 68.54, QED 0.3
Compound (SMILES): COc1cccc2c(C(=O)OCC34CCN(CC3)CC4)c[nH]c12
InChIKey: RIZNRXQIXARGMI-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Cytochrome P450 Inhibition: Protocol 2: Stock solution for NCEs (test articles) and standard inhibitors were prepared at a concentration of 20 mM in DMSO. Stock solutions were diluted with DMSO to get substocks which were further diluted 10-fold in 80:20 MeCN:water to obtain intermediate substocks. Working stocks were prepared by diluting the intermediate substocks 50-fold in buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 314.39, ALogP 2.82, HBA 4, HBD 1, PSA 54.56, QED 0.88
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1csnn1
InChIKey: KDMBMLINAPXLCW-UZLBHIALSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Activity at human muscarinic acetylcholine receptor M3 transfected in CHO-K1 cells assessed as intracellular calcium levels in presence of acetylcholine by FLIPR assay
Measurement: Ki = 275.42 nM (pChEMBL 6.559999942779541)
Descriptors: MW 480.59, ALogP 4.71, HBA 8, HBD 0, PSA 59.73, QED 0.36
Compound (SMILES): CC(=O)SC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: FNTDWLPCWWDDJQ-HAQNSBGRSA-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 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 329.43, ALogP 3.16, HBA 6, HBD 1, PSA 75.94, QED 0.8
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc3ncccc3o2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RYLYPXANRHKWKH-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 = 14.45 nM (pChEMBL 7.840000152587891)
Descriptors: MW 492.54, ALogP 5.53, HBA 9, HBD 0, PSA 91.33, QED 0.29
Compound (SMILES): COc1ncnc(N2Cc3cn(-c4cccc(S(C)(=O)=O)c4)nc3[C@H]2C(C)C)c1F
InChIKey: XOTHLYNSDMSVGX-GOSISDBHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 1445 nM (pChEMBL 5.840000152587891)
Descriptors: MW 431.49, ALogP 2.93, HBA 8, HBD 0, PSA 90.21, QED 0.61
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(F)c(C(F)(F)F)c4F)cs3)csc2n(C)c1=O
InChIKey: XOPMVFNBFICPDB-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NET8
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 = 2520 nM (pChEMBL 5.599999904632568)
Descriptors: MW 516.47, ALogP 3.9, HBA 8, HBD 1, PSA 85.99, QED 0.42
Compound (SMILES): Cc1nccn1-c1ccc(-c2cn(CC(=O)Nc3cccc(Cl)c3Cl)nn2)cc1
InChIKey: XSIJYOFJNDFHGL-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin)
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 427.3, ALogP 4.38, HBA 6, HBD 1, PSA 77.63, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CCNCC(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NEDQSDMNOSMYHF-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 = 1.38 nM (pChEMBL 8.859999656677246)
Descriptors: MW 468.51, ALogP 4.04, HBA 8, HBD 1, PSA 77.33, QED 0.35
Compound (SMILES): CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4ccc(C(F)(F)F)cc4Cl)oc23)[C@@H]1CO
InChIKey: MRPGRAKIAJJGMM-OCCSQVGLSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of human CDK4
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 469.84, ALogP 4.32, HBA 6, HBD 3, PSA 94.14, QED 0.53
Compound (SMILES): O=C(O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(O)Cc2cccc(Br)c2)cc1
InChIKey: JQSUCRMHKFCGBV-FSKZSRKQSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: cAMP Assay: A 384-well drug plate was prepared to contain test compounds, PGE2 and cAMP in 16 serial dilutions in triplicate, using a Biomek station. HEK-EBNA cells expressing a target PG receptor subtype (EP2 or EP4) were suspended in a stimulation buffer (HBSS, 0.1% BSA, 0.5 mM IBMX and 5 mM HEPES, pH 7.4) in a density of 104 cells/5 μl. The reaction was initiated by mixing 5 μL drug dilutions with 5 μl of HEK-EBNA cells in a well, carried out for 30 min at room temperature, and followed by the addition of 5 μl anti-cAMP acceptor beads in the control buffer with Tween-20 (25 mM NaCl, 0.03% Tween-20, 5 mM HEPES, pH7.4). After 30 min in the dark at room temperature, the mixtures were incubated with 15 μl biotinylated-cAMP/strpavidin donor beads in Lysis/Detection buffer (0.1% BSA, 0.3% Tween-20 and 5 mM HEPES, pH7.4) for 45 min at the room temperature. Fluorescence changes were read using a Fusion-alpha HT microplate reader.
Measurement: EC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 457.36, ALogP 4.84, HBA 3, HBD 2, PSA 74.6, QED 0.56
Compound (SMILES): Cc1cc(Br)c2c(C(=O)OCC34CCN(CC3)CC4)c[nH]c2c1
InChIKey: YAFIJFYBHSPFCK-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 377.28, ALogP 3.88, HBA 3, HBD 1, PSA 45.33, QED 0.83
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc(OC(F)(F)F)ccc12
InChIKey: WIKZEYZKRGVBAV-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Cytochrome P450 Inhibition: Protocol 2: Stock solution for NCEs (test articles) and standard inhibitors were prepared at a concentration of 20 mM in DMSO. Stock solutions were diluted with DMSO to get substocks which were further diluted 10-fold in 80:20 MeCN:water to obtain intermediate substocks. Working stocks were prepared by diluting the intermediate substocks 50-fold in buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 368.36, ALogP 3.71, HBA 4, HBD 1, PSA 54.56, QED 0.84
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C5CN(CCO)C5)c4)nc3c2)c1
InChIKey: HPCVPAAIFAFKQL-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 = 4.169 nM (pChEMBL 8.380000114440918)
Descriptors: MW 500.6, ALogP 3.91, HBA 9, HBD 1, PSA 88.77, QED 0.35
Compound (SMILES): CCOCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: UEQFXSRKEVOHTE-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 433.51, ALogP 4.22, HBA 8, HBD 0, PSA 74.53, QED 0.37
Compound (SMILES): COC(=O)c1ccnc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)n1
InChIKey: LNDDPQBVBYCMAP-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 = 20.42 nM (pChEMBL 7.690000057220459)
Descriptors: MW 535.56, ALogP 3.81, HBA 11, HBD 0, PSA 117.38, QED 0.22
Compound (SMILES): NC1CCC(N[C@@H]2C[C@H]2c2ccccc2)CC1
InChIKey: ALHBJBCQLJZYON-PFSRBDOWSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescence-Based (Inhibitor)-Screening Assay: In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescence-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropanamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAO-A and MAO-B activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in duplicate within the same experiment.Briefly, a fixed amount of MAO (0.25 ug for MAO-A and 0.5 ug for MAO-B) was incubated on ice for 15 minutes in the reaction buffer, in the absence and/or in the presence of at least eight 3-fold serial dilutions each. Clorgyline and Deprenyl (Sigma Aldrich) was used as a control for specific inhibition of MAO-A and MAO-B respectively. After leaving the enzyme(s) interacting with the inhibitor, KM of kynuramine was added to each reaction for MAO-B and MAO-A assay respectively, and the reaction was left for 1 hour at 37° C. in the dark. The oxidative deamination of the substrate was stopped by adding 50 uL of NaOH 2N. The conversion of kynuramine to 4-hydroxyquinoline, was monitored by fluorescence (excitation at 320 nm, emission at 360 nm) using a microplate reader (Infinite 200, Tecan). Arbitrary units were used to measure levels of fluorescence produced in the absence and/or in the presence of inhibitor. The maximum of oxidative deamination activity was obtained by measuring the amount of 4-hydroxyquinoline formed from kynuramine deamination in the absence of inhibitor and corrected for background fluorescence in the absence of MAO enzymes. The IC50 values of each inhibitor were calculated with GraphPad Prism Software.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 230.35, ALogP 2.4, HBA 2, HBD 2, PSA 38.05, QED 0.84
Compound (SMILES): [2H]C([2H])([2H])Oc1cc(OC([2H])([2H])[2H])cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C([2H])([2H])C([2H])([2H])C([2H])([2H])O)c1
InChIKey: MLUFVERLBQGOEV-KDUMBFBCSA-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 = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 419.49, ALogP 3.57, HBA 8, HBD 1, PSA 85.53, QED 0.47
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)C(C)(O)CCC[C@H](N1CCC(c3c(F)ccc(Cl)c3F)=CC1=O)c1cc-2ccn1
InChIKey: WTXJOYYHXJPKFK-ZGAORZAOSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition Assay: Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4 containing 145 mM NaCl, 5 mM KCl, and 0.1% PEG 8000 (polyethylene glycol; JT Baker or Fisher Scientific). Determinations were made using purified human Factor XIa at a final concentration of 25-200 pM (Haematologic Technologies) and the synthetic substrate S-2366 (pyroGlu-Pro-Arg-pNA; CHROMOGENIX® or AnaSpec) at a concentration of 0.0002-0.001 M.
Measurement: Ki = 20.1 nM (pChEMBL 7.699999809265137)
Descriptors: MW 611.05, ALogP 6.09, HBA 6, HBD 3, PSA 120.86, QED 0.31
Compound (SMILES): N#Cc1ccc(S(=O)(=O)Nc2ccc(-c3nc4cc(NS(=O)(=O)c5ccc(C#N)cc5)ccc4o3)cc2)cc1
InChIKey: SXDQOZITTMTZPM-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 555.6, ALogP 4.84, HBA 8, HBD 2, PSA 165.95, QED 0.29
Compound (SMILES): Cc1c[nH]c2ncc(-c3cccc(NC(=O)/C=C/CN(C)C)c3)cc12
InChIKey: POFBZQXDWPOYEW-VMPITWQZSA-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 334.42, ALogP 3.59, HBA 3, HBD 2, PSA 61.02, QED 0.7
Compound (SMILES): CCN1CCCC1c1nc(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)no1
InChIKey: OUPSOAXLJSDWRF-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 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 515.4, ALogP 5.81, HBA 9, HBD 1, PSA 98.43, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)s2)c2ccc3ncc(-c4cnn(CCN5CCNCC5)c4)nc3c2)c1.Cl
InChIKey: NEZTVLXEJBQTPI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.311 nM (pChEMBL 8.479999542236328)
Descriptors: MW 590.15, ALogP 5.47, HBA 10, HBD 1, PSA 80.57, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(C/C=C/c2cc(C)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: FFRZNGZQCMXHFG-AATRIKPKSA-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 = 46.77 nM (pChEMBL 7.329999923706055)
Descriptors: MW 492.58, ALogP 5.6, HBA 8, HBD 0, PSA 78.19, QED 0.28
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1noc(C2CCCCN2C(=O)OC(C)(C)C)n1
InChIKey: RUBSXJGCJAOKHK-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 601.49, ALogP 7.11, HBA 10, HBD 1, PSA 124.73, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(Cc2cn[nH]n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BMRGVWYMLHCENU-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 442.48, ALogP 3.5, HBA 9, HBD 1, PSA 106.87, QED 0.41
Compound (SMILES): CC(C)N1CCN(c2ccc(Nc3ncc4cc5n(c4n3)C3(CCCCC3)CNC5=O)nc2)CC1
InChIKey: YPJRHEKCFKOVRT-UHFFFAOYSA-N
Target: NUAK family SNF1-like kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H093
Assay: Binding affinity to SNARK (unknown origin)
Measurement: Kd = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 474.61, ALogP 3.5, HBA 8, HBD 2, PSA 91.21, QED 0.6
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(S(=O)(=O)NC)cc4)cc23)c1F
InChIKey: LHCPHGXHCUEJNV-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 548.59, ALogP 3.8, HBA 6, HBD 3, PSA 138.09, QED 0.27
Compound (SMILES): CC(C)N1CCC(NC(=O)c2cc3ccccc3n2CC(=O)Nc2ccc(Br)cc2)CC1
InChIKey: YGFYVRAFMFBVHU-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 = 2.87 nM (pChEMBL 8.539999961853027)
Descriptors: MW 497.44, ALogP 4.65, HBA 4, HBD 2, PSA 66.37, QED 0.52
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: ONFWLPPHDKCNSS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.38 nM (pChEMBL 8.859999656677246)
Descriptors: MW 486.62, ALogP 5.06, HBA 8, HBD 0, PSA 68.54, QED 0.33
Compound (SMILES): Cc1cnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4c(F)cccc4F)c3F)c2c1
InChIKey: HCTZYODXCHNCIP-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 463.41, ALogP 4.46, HBA 4, HBD 2, PSA 91.92, QED 0.34
Compound (SMILES): Cn1cc(-c2cnc3ccc(N(CCCNCC(F)(F)F)c4cc(Cl)cc(Cl)c4)cc3n2)cn1
InChIKey: IZRLMSOUCGWVLU-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 = 436.52 nM (pChEMBL 6.360000133514404)
Descriptors: MW 509.36, ALogP 6.02, HBA 6, HBD 1, PSA 58.87, QED 0.29
Compound (SMILES): CCOC(=O)C1CCN(CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)CC1
InChIKey: LCIPUHSYYUXUFV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.388 nM (pChEMBL 8.470000267028809)
Descriptors: MW 544.66, ALogP 4.46, HBA 10, HBD 0, PSA 94.84, QED 0.27
Compound (SMILES): CCOC(=O)Cn1cc(CN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)nn1
InChIKey: WRSADQAXUUZHPM-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 = 19.5 nM (pChEMBL 7.710000038146973)
Descriptors: MW 528.57, ALogP 3.54, HBA 12, HBD 0, PSA 122.31, QED 0.25
Compound (SMILES): COc1cc(OC)cc(N(CCn2cc(C)nc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: KFJVJRYTWRDUKS-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 = 60.26 nM (pChEMBL 7.21999979019165)
Descriptors: MW 483.58, ALogP 4.7, HBA 9, HBD 0, PSA 83.12, QED 0.32
Compound (SMILES): C[C@@H]1c2ncn(-c3ccc(F)cc3)c2CCN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: SNHBVDDINCFQMQ-GFCCVEGCSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate after 15 mins by LC/MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 437.82, ALogP 5.44, HBA 3, HBD 0, PSA 38.13, QED 0.5
Compound (SMILES): CN1C(=O)c2ccccc2N(C)c2nc(Nc3cccc(S(N)(=O)=O)c3)ncc21
InChIKey: KCMYPBPMTXEKNF-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: In Vitro Kinase Assay: The enzymatic activities against PI3K-α, PI3K-β, PI3K-γ and PI3K-δ were tested in ADAPTA assays. Activity against AURKB and AURKB were tested in Z′-Lyte assays. All assays were performed with ATP concentrations of Km for each kinase. BRD4_1 binding was tested using an AlphaScreen assay. All protocols are available from Life Technologies.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 410.46, ALogP 2.23, HBA 7, HBD 2, PSA 121.52, QED 0.68
Compound (SMILES): O=C(O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(O)Cc2ccccc2F)cc1
InChIKey: ABNHKWJQNLIOML-YILGNFQOSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Radioligand Binding Assay: The cell homogenate was centrifuged at 19000 r.p.m. for 20 min at 4° C. using a Beckman Ti-60 rotor. The resultant pellet was resuspended in TME buffer to give a final 1 mg/ml protein concentration, as determined by Biorad assay. Radioligand binding competition assays vs. [3H-]17-phenyl PGF2a , (5 nM) were performed in a 100 μl volume for 60 min. Binding reactions were started by adding plasma membrane fraction. The reaction was terminated by the addition of 4 ml ice-cold TRIS-HCl buffer and rapid filtration through glass fiber GF/B filters using a Brandel cell harvester. The filters were washed 3 times with ice-cold buffer and oven dried for one hour. [3H-] PGE2 (specific activity 180 Ci mmol) was used as the radioligand for EP receptors. [3H] 17-phenyl PGF2a, was employed for FP receptor binding studies. Binding studies employing EP1, EP2, EP4 and FP receptors were performed in duplicate in at least three separate experiments. A 200 μl assay volume was used. Incubations w
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 396.46, ALogP 4.21, HBA 3, HBD 2, PSA 74.6, QED 0.66
Compound (SMILES): COc1ncc(-c2cnc3[nH]cc(C(=O)c4c(F)ccc(NS(=O)(=O)c5cc(F)ccc5F)c4F)c3c2)cn1
InChIKey: HNZHVLFQWSISBO-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 557.49, ALogP 4.62, HBA 7, HBD 2, PSA 126.93, QED 0.22
Compound (SMILES): COc1ccc(CCC(=O)NS(=O)(=O)C(F)(F)F)c(CN2CCC[C@H]2c2nc(C(=O)NCCCCC3CCCCC3)co2)c1
InChIKey: ZBYCYKAOQOIIRO-SANMLTNESA-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 642.74, ALogP 5.4, HBA 8, HBD 2, PSA 130.84, QED 0.26
Compound (SMILES): COc1cccc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XKYKMEFXVHYFRM-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 = 38.9 nM (pChEMBL 7.409999847412109)
Descriptors: MW 375.43, ALogP 3.17, HBA 7, HBD 1, PSA 76.3, QED 0.56
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCN(C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WZWCHRIODAFYKY-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 = 2.57 nM (pChEMBL 8.59000015258789)
Descriptors: MW 487.61, ALogP 3.43, HBA 9, HBD 0, PSA 71.78, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(CCc2nnn[nH]2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YMXQQOATOHFDLF-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 = 7.413 nM (pChEMBL 8.130000114440918)
Descriptors: MW 457.5, ALogP 2.94, HBA 10, HBD 1, PSA 119.76, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H](O)C(F)(F)F)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: JXGGHGLZZYBWNG-XMMPIXPASA-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 = 5.888 nM (pChEMBL 8.229999542236328)
Descriptors: MW 501.51, ALogP 5.15, HBA 8, HBD 1, PSA 85.53, QED 0.36
Compound (SMILES): CCC(=O)N1CC[C@H](Oc2ccnc3ccc(-c4ccc(OC)nc4)cc23)C1
InChIKey: GKVUBNGBTYQPGF-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of myristoylated PI3K-beta (unknown origin) overexpressed in Rat1 cells assessed as inhibition of Akt phosphorylation
Measurement: IC50 = 877 nM (pChEMBL 6.059999942779541)
Descriptors: MW 377.44, ALogP 3.7, HBA 5, HBD 0, PSA 64.55, QED 0.68
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCCC2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: SIWFRERSMYFRNO-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 = 2.512 nM (pChEMBL 8.600000381469727)
Descriptors: MW 500.65, ALogP 5.45, HBA 8, HBD 0, PSA 68.54, QED 0.3
Compound (SMILES): CC(=O)SC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: FNTDWLPCWWDDJQ-HAQNSBGRSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 329.43, ALogP 3.16, HBA 6, HBD 1, PSA 75.94, QED 0.8
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc3ncccc3o2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RYLYPXANRHKWKH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 12.88 nM (pChEMBL 7.889999866485596)
Descriptors: MW 492.54, ALogP 5.53, HBA 9, HBD 0, PSA 91.33, QED 0.29
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(F)c(C(F)(F)F)c4F)cs3)csc2n(C)c1=O
InChIKey: XOPMVFNBFICPDB-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 = 4570 nM (pChEMBL 5.340000152587891)
Descriptors: MW 516.47, ALogP 3.9, HBA 8, HBD 1, PSA 85.99, QED 0.42
Compound (SMILES): Cc1nccn1-c1ccc(-c2cn(CC(=O)Nc3cccc(Cl)c3Cl)nn2)cc1
InChIKey: XSIJYOFJNDFHGL-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 427.3, ALogP 4.38, HBA 6, HBD 1, PSA 77.63, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CCNCC(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NEDQSDMNOSMYHF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 468.51, ALogP 4.04, HBA 8, HBD 1, PSA 77.33, QED 0.35
Compound (SMILES): CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4ccc(C(F)(F)F)cc4Cl)oc23)[C@@H]1CO
InChIKey: MRPGRAKIAJJGMM-OCCSQVGLSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: Inhibition of human CDK6
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 469.84, ALogP 4.32, HBA 6, HBD 3, PSA 94.14, QED 0.53
Compound (SMILES): O=C(O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(O)Cc2cccc(Br)c2)cc1
InChIKey: JQSUCRMHKFCGBV-FSKZSRKQSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: cAMP Assay: A 384-well drug plate was prepared to contain test compounds, PGE2 and cAMP in 16 serial dilutions in triplicate, using a Biomek station. HEK-EBNA cells expressing a target PG receptor subtype (EP2 or EP4) were suspended in a stimulation buffer (HBSS, 0.1% BSA, 0.5 mM IBMX and 5 mM HEPES, pH 7.4) in a density of 104 cells/5 μl. The reaction was initiated by mixing 5 μL drug dilutions with 5 μl of HEK-EBNA cells in a well, carried out for 30 min at room temperature, and followed by the addition of 5 μl anti-cAMP acceptor beads in the control buffer with Tween-20 (25 mM NaCl, 0.03% Tween-20, 5 mM HEPES, pH7.4). After 30 min in the dark at room temperature, the mixtures were incubated with 15 μl biotinylated-cAMP/strpavidin donor beads in Lysis/Detection buffer (0.1% BSA, 0.3% Tween-20 and 5 mM HEPES, pH7.4) for 45 min at the room temperature. Fluorescence changes were read using a Fusion-alpha HT microplate reader.
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 457.36, ALogP 4.84, HBA 3, HBD 2, PSA 74.6, QED 0.56
Compound (SMILES): Cc1cc(Br)c2c(C(=O)OCC34CCN(CC3)CC4)c[nH]c2c1
InChIKey: YAFIJFYBHSPFCK-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 377.28, ALogP 3.88, HBA 3, HBD 1, PSA 45.33, QED 0.83