lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2c1OC
InChIKey: MHHANWALJYYOEO-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 344.41, ALogP 2.83, HBA 5, HBD 1, PSA 63.79, QED 0.85
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: MMGNRRUXETXMDE-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 447.54, ALogP 4.61, HBA 8, HBD 1, PSA 85.53, QED 0.4
Compound (SMILES): CCCCCC(O)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)s2)cc1
InChIKey: NGKFLYGSJDSBQC-QSVWIEALSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at human recombinant EP2 receptor expressed in HEK-EBNA cells incubated for 30 mins by cAMP accumulation assay
Measurement: EC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 431.55, ALogP 4.77, HBA 5, HBD 2, PSA 87.07, QED 0.5
Compound (SMILES): Cc1ccc(CN2CC[C@@H](N3CC[C@@H](c4ccc(O)cc4)[C@H](F)C3)C2=O)cc1
InChIKey: UNVYDSCXINFREZ-BHDDXSALSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 382.48, ALogP 3.63, HBA 3, HBD 1, PSA 43.78, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: WPAMXPNNWJGKNP-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 449.51, ALogP 3.02, HBA 9, HBD 2, PSA 105.76, QED 0.38
Compound (SMILES): NC(=O)c1cccc(-c2c[nH]c3ncnc(N4CCOCC4)c23)c1
InChIKey: NCXSLSJEOUOJBB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Displacement of K5 tracer from full length C-terminal NanoLuc fused human STK4 expressed in HEK293T cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 259 nM (pChEMBL 6.590000152587891)
Descriptors: MW 323.36, ALogP 1.56, HBA 5, HBD 2, PSA 97.13, QED 0.76
Compound (SMILES): COc1cc(OC)cc(N(CC2CCN(C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BXMUZNHPFQUNSZ-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 472.59, ALogP 4.53, HBA 8, HBD 0, PSA 68.54, QED 0.39
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1c(-c2c(Cl)cccc2Cl)noc1C
InChIKey: AHIOWTSQFILAEW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
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 576.27, ALogP 8.54, HBA 7, HBD 1, PSA 82.3, QED 0.21
Compound (SMILES): C[C@@H](c1nc2ccc(N3CCC[C@@H](C(=O)N4CCCC4)C3)nc2[nH]1)n1cc(Cl)cn1
InChIKey: NOSUIOGIJKVTAO-LSDHHAIUSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: In Vitro DGAT2 Assay: For determination of IC50 values, the reactions were carried out in 384-well white Polyplates (Perkin Elmer) in a total volume of 20 uL. To 1 uL of compounds dissolved in 100% DMSO and spotted at the bottom of each well, 5 uL of 0.04% bovine serum albumin (BSA) (fatty acid free, Sigma Aldrich) was added and the mixture was incubated at room temperature for 20 minutes. To this mixture, 10 uL of hDGAT2 membrane fraction (0.01 mg/mL) diluted in 100 mM Hepes-NaOH, pH 7.4, 20 mM MgCl2 containing 200 nM methyl arachidonyl fluorophosphonate (Cayman Chemical; dried from ethyl acetate stock solution under argon gas and dissolved in DMSO as 5 mM stock) was added. After this mixture was preincubated at room temperature for 2 hours, DGAT2 reactions were initiated by the addition of 4 uL of substrates containing 30 uM [1-14C]decanoyl-CoA (custom-synthesized by Perkin Elmer, 50 mCi/mmol) and 125 uM 1,2-didecanoyl-sn-glycerol (Avanti Polar Lipids) dissolved in 12.5% acetone. The reaction mixtures were incubated at room temperature for 40 min and the reactions were stopped by addition of 5 uL of 1% H3PO4. After the addition of 45 uL MicroScint-E (Perkin-Elmer), plates were sealed with Top Seal-A covers (Perkin-Elmer) and phase partitioning of substrates and products was achieved using a HT-91100 microplate orbital shaker (Big Bear Automation, Santa Clara, Calif.). Plates were centrifuged at 2,000×g for 1 min in an Allegra 6R Centrifuge (Beckman Coulter) and then were sealed again with fresh covers before reading in a 1450 Microbeta Wallac Trilux Scintillation Counter (Perkin Elmer). DGAT2 activity was measured by quantifying the generated product [14C]tridecanoylglycerol in the upper organic phase.
Measurement: IC50 = 14.5 nM (pChEMBL 7.840000152587891)
Descriptors: MW 427.94, ALogP 3.26, HBA 6, HBD 1, PSA 82.94, QED 0.69
Compound (SMILES): O=C(c1c(F)ccc(NS(=O)(=O)c2cccnc2)c1F)c1c[nH]c2nccc(Cl)c12
InChIKey: UGHOYILAXQCULM-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 448.84, ALogP 3.92, HBA 5, HBD 2, PSA 104.81, QED 0.45
Compound (SMILES): CCn1cc(-c2cnc3ccc(N(CCNC)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: ZNKBNXVWLPQHKJ-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 = 3.548 nM (pChEMBL 8.449999809265137)
Descriptors: MW 432.53, ALogP 3.89, HBA 8, HBD 1, PSA 77.33, QED 0.43
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCO)c3)nc2c1
InChIKey: CQDXYQFRLSRPQH-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 = 15.14 nM (pChEMBL 7.820000171661377)
Descriptors: MW 448.53, ALogP 2.86, HBA 9, HBD 2, PSA 97.56, QED 0.38
Compound (SMILES): CCSC[C@@](O)([C@@H](Nc1cccc2nc(C)ccc12)c1ccc(OC)c(F)c1Cl)C(F)(F)F
InChIKey: NVBRVAKHESDYFE-FCHUYYIVSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at glucocorticoid receptor in human ChaGoK1 cells assessed as inhibition of AP1-mediated transcriptional activity by measuring reduction in PMA-stimulated TRE-LacZ activity after 24 hrs in presence of MUG by fluorometric assay
Measurement: IC50 = 0.47 nM (pChEMBL 9.329999923706055)
Descriptors: MW 502.96, ALogP 6.54, HBA 5, HBD 2, PSA 54.38, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCNS(=O)(=O)N(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HONWIFHKRIBHLZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of TEL-fused FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 72 hrs by Alamar blue assay
Measurement: IC50 = 0.8913 nM (pChEMBL 9.050000190734863)
Descriptors: MW 525.64, ALogP 2.97, HBA 9, HBD 1, PSA 114.71, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@@H]1CO[C@H]2[C@@H]1OC[C@@H]2OC
InChIKey: VENHPOQTVRCHJV-JXBRRONGSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 492.36, ALogP 4.5, HBA 8, HBD 1, PSA 83.96, QED 0.52
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3ccccn3)c2c(=O)n1-c1ccccc1
InChIKey: RYAQYDFEDXGXQC-FQEVSTJZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition Assays: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110δ/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 μg/mL). Reactions are initiated by the addition of ATP containing 10 μCi of γ-32P-ATP to a final concentration of 10 or 100 μM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 μL 1N HCl followed by 160 μL CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 525.57, ALogP 3.9, HBA 8, HBD 2, PSA 120.2, QED 0.34
Compound (SMILES): O=C(c1ccc2cc(Oc3ccc(C(F)F)cn3)ccc2n1)N1CCNCC1
InChIKey: XJNLQAUECWCBNY-UHFFFAOYSA-N
Target: Sodium channel protein type 2 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q99250
Assay: Inhibition of recombinant human Nav1.2 expressed in HEK293 cells incubated for 3 mins by FRET based membrane potential assay
Measurement: IC50 = 12800 nM (pChEMBL 4.889999866485596)
Descriptors: MW 384.39, ALogP 3.41, HBA 5, HBD 1, PSA 67.35, QED 0.75
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ncccc2OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IHZFSYQVOKXLQL-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 = 48.98 nM (pChEMBL 7.309999942779541)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(C2CCCNC2)n1
InChIKey: HFTHZTJJBJKTGD-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 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 516.45, ALogP 6.19, HBA 8, HBD 2, PSA 81.19, QED 0.3
Compound (SMILES): COc1ccc(NC(=O)C2=C(c3ccc(C)cc3)C[C@](c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)NC2=O)cc1
InChIKey: FBBPRPJENPWDPL-LJAQVGFWSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Mus musculus
UniProt: Q921V5
Assay: Inhibition of mouse MGAT2 in mouse STC-1 cell based assay
Measurement: IC50 = 0.58 nM (pChEMBL 9.239999771118164)
Descriptors: MW 606.56, ALogP 7.09, HBA 4, HBD 2, PSA 76.66, QED 0.15
Compound (SMILES): COc1cc(O)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ZXPUNZSPQJIHJB-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 = 5.248 nM (pChEMBL 8.279999732971191)
Descriptors: MW 432.53, ALogP 3.88, HBA 8, HBD 2, PSA 88.33, QED 0.44
Compound (SMILES): CCN(C)Cc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PVNKKQPQLLGLMA-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.59, ALogP 5.04, HBA 7, HBD 0, PSA 59.31, QED 0.35
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(N)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PFFKWQNVRNBIGB-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 = 3.02 nM (pChEMBL 8.520000457763672)
Descriptors: MW 487.61, ALogP 3.61, HBA 9, HBD 1, PSA 94.56, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1.Cl
InChIKey: NDXCOBYSTJUJJD-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 = 1.698 nM (pChEMBL 8.770000457763672)
Descriptors: MW 474.61, ALogP 5.23, HBA 8, HBD 1, PSA 77.33, QED 0.34
Compound (SMILES): CC(C)(C)OC(=O)N1CCC2(CC1)CC2CNC(=O)N1Cc2ccncc2C1
InChIKey: DLHHFYXNVIMXSY-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Biochemical Inhibition Assay: The NAMPT enzymatic reactions were carried out in Buffer A (50 mM Hepes pH 17.5, 50 mM NaCl, 5 mM MgCl2, and 1 mM THP) in 96-well V-bottom plates. The compound titrations were performed in a separate dilution plate by serially diluting the compounds in DMSO to make a 100× stock. Buffer A (89 μL) containing 33 nM of NAMPT protein was added to 1 μL of 100× compound plate containing controls (e.g. DMSO or blank). The compound and enzyme mixture was incubated for 15 min at room temperature, then 10 μL of 10× substrate and co-factors in Buffer A were added to the test well to make a final concentration of 1 μM NAM, 100 μM 5-Phospho-D-ribose 1-diphosphate (PRPP), and 2.5 mM Adenosine 5′-triphosphate (ATP). The reaction was allowed to proceed for 30 min at room temperature, then was quenched with the addition of 11 μL of a solution of formic acid and L-Cystathionine to make a final concentration of 1% formic acid and 10 μM L-Cystathionine Background and signal strength was determined by addition (or non-addition) of a serial dilution of NMN to a pre-quenched enzyme and cofactor mix.
Measurement: IC50 = 6.36 nM (pChEMBL 8.199999809265137)
Descriptors: MW 386.5, ALogP 3.14, HBA 4, HBD 1, PSA 74.77, QED 0.85
Compound (SMILES): Cc1ccc(OCCNc2nc(Nc3cc(C)[nH]n3)cc(C)c2C#N)cn1
InChIKey: BOWYXGHFMQMXPT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Inhibition of LYN (unknown origin)
Measurement: Ki = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 363.43, ALogP 3.23, HBA 7, HBD 3, PSA 111.54, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CCNC[Si](C)(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: JMKXJKVYUUVONH-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 = 4.786 nM (pChEMBL 8.319999694824219)
Descriptors: MW 490.68
Compound (SMILES): COC(=N)c1nc2ccc3ncnc(Nc4ccc(OC)cc4F)c3c2s1
InChIKey: RYBNARZBIXTFJS-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of CLK1 (unknown origin)
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 383.41, ALogP 4.1, HBA 8, HBD 2, PSA 93.01, QED 0.41
Compound (SMILES): Cc1ncccc1-n1c([C@H](C)Nc2nc(N)nc(N)c2C#N)nc2cccc(Cl)c2c1=O
InChIKey: MODOHQQWQXQEQB-NSHDSACASA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal His-tagged PI3K p110beta/p85alpha using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 447.89, ALogP 2.74, HBA 10, HBD 3, PSA 161.42, QED 0.43
Compound (SMILES): CCOc1ccnc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)n1
InChIKey: PRVGMAOUBRLMGU-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 = 9.55 nM (pChEMBL 8.020000457763672)
Descriptors: MW 521.58, ALogP 4.43, HBA 10, HBD 0, PSA 100.31, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(O)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JMBVTEKOAZJGIC-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 = 1.95 nM (pChEMBL 8.710000038146973)
Descriptors: MW 511.54, ALogP 3.92, HBA 10, HBD 2, PSA 127.52, QED 0.32
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccn(C)c(=O)c1
InChIKey: JVGDBVAGMMZAGB-YKSBVNFPSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in microsomes using ER as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 503.59, ALogP 4.56, HBA 7, HBD 0, PSA 55.95, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4cc5n(c4n3)C3(CCCCC3)CNC5=O)nc2)CC1
InChIKey: PDGKHKMBHVFCMG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of human CDK2/cyclin E
Measurement: EC50 < 100 nM (pChEMBL 7)
Descriptors: MW 446.56, ALogP 2.72, HBA 8, HBD 2, PSA 91.21, QED 0.64
Compound (SMILES): COc1cc(OC)c(F)c(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1F
InChIKey: GLLVJFAKHOOPKT-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 = 2.089 nM (pChEMBL 8.680000305175781)
Descriptors: MW 536.51, ALogP 5.01, HBA 8, HBD 1, PSA 77.33, QED 0.23
Compound (SMILES): O=C(Nc1ccc(F)cc1)N1N=C(c2ccncc2)CC1c1ccc(F)cc1
InChIKey: RDQXNTXNNZITKD-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1I (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0X4
Assay: Inhibition of human T-type calcium channel Cav3.3 expressed in CHO cells assessed as inhibition of calcium tail current at -60 mV holding potential measured after 150 secs by QPatch assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 378.38, ALogP 4.74, HBA 3, HBD 1, PSA 57.59, QED 0.72
Compound (SMILES): COC/C(CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1)=N/O
InChIKey: YIDCCLXYFLNYHA-OGLMXYFKSA-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 = 6.026 nM (pChEMBL 8.220000267028809)
Descriptors: MW 462.51, ALogP 3.66, HBA 10, HBD 1, PSA 107.12, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: MMGNRRUXETXMDE-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 = 0.7079 nM (pChEMBL 9.149999618530273)
Descriptors: MW 447.54, ALogP 4.61, HBA 8, HBD 1, PSA 85.53, QED 0.4
Compound (SMILES): Cc1ccc(CN2CC[C@@H](N3CC[C@@H](c4ccc(O)cc4)[C@H](F)C3)C2=O)cc1
InChIKey: UNVYDSCXINFREZ-BHDDXSALSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 382.48, ALogP 3.63, HBA 3, HBD 1, PSA 43.78, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: WPAMXPNNWJGKNP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.479 nM (pChEMBL 8.829999923706055)
Descriptors: MW 449.51, ALogP 3.02, HBA 9, HBD 2, PSA 105.76, QED 0.38
Compound (SMILES): NC(=O)c1cccc(-c2c[nH]c3ncnc(N4CCOCC4)c23)c1
InChIKey: NCXSLSJEOUOJBB-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Displacement of K5 tracer from full length C-terminal NanoLuc fused human LRRK2 expressed in HEK293T cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 2360 nM (pChEMBL 5.630000114440918)
Descriptors: MW 323.36, ALogP 1.56, HBA 5, HBD 2, PSA 97.13, QED 0.76
Compound (SMILES): COc1cc(OC)cc(N(CC2CCN(C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BXMUZNHPFQUNSZ-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 472.59, ALogP 4.53, HBA 8, HBD 0, PSA 68.54, QED 0.39
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1c(-c2c(Cl)cccc2Cl)noc1C
InChIKey: AHIOWTSQFILAEW-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 576.27, ALogP 8.54, HBA 7, HBD 1, PSA 82.3, QED 0.21
Compound (SMILES): C[C@@H](c1nc2ccc(N3CCC[C@@H](C(=O)N4CCCC4)C3)nc2[nH]1)n1cc(Cl)cn1
InChIKey: NOSUIOGIJKVTAO-LSDHHAIUSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: In Vitro DGAT2 Assay: For determination of IC50 values, the reactions were carried out in 384-well white Polyplates (Perkin Elmer) in a total volume of 20 uL. To 1 uL of compounds dissolved in 100% DMSO and spotted at the bottom of each well, 5 uL of 0.04% bovine serum albumin (BSA) (fatty acid free, Sigma Aldrich) was added and the mixture was incubated at room temperature for 20 minutes. To this mixture, 10 uL of hDGAT2 membrane fraction (0.01 mg/mL) diluted in 100 mM Hepes-NaOH, pH 7.4, 20 mM MgCl2 containing 200 nM methyl arachidonyl fluorophosphonate (Cayman Chemical; dried from ethyl acetate stock solution under argon gas and dissolved in DMSO as 5 mM stock) was added. After this mixture was preincubated at room temperature for 2 hours, DGAT2 reactions were initiated by the addition of 4 uL of substrates containing 30 uM [1-14C]decanoyl-CoA (custom-synthesized by Perkin Elmer, 50 mCi/mmol) and 125 uM 1,2-didecanoyl-sn-glycerol (Avanti Polar Lipids) dissolved in 12.5% acetone. The reaction mixtures were incubated at room temperature for 40 min and the reactions were stopped by addition of 5 uL of 1% H3PO4. After the addition of 45 uL MicroScint-E (Perkin-Elmer), plates were sealed with Top Seal-A covers (Perkin-Elmer) and phase partitioning of substrates and products was achieved using a HT-91100 microplate orbital shaker (Big Bear Automation, Santa Clara, Calif.). Plates were centrifuged at 2,000×g for 1 min in an Allegra 6R Centrifuge (Beckman Coulter) and then were sealed again with fresh covers before reading in a 1450 Microbeta Wallac Trilux Scintillation Counter (Perkin Elmer). DGAT2 activity was measured by quantifying the generated product [14C]tridecanoylglycerol in the upper organic phase.
Measurement: IC50 = 38.5 nM (pChEMBL 7.420000076293945)
Descriptors: MW 427.94, ALogP 3.26, HBA 6, HBD 1, PSA 82.94, QED 0.69
Compound (SMILES): O=C(c1c(F)ccc(NS(=O)(=O)c2cccnc2)c1F)c1c[nH]c2nccc(Cl)c12
InChIKey: UGHOYILAXQCULM-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 448.84, ALogP 3.92, HBA 5, HBD 2, PSA 104.81, QED 0.45
Compound (SMILES): CCn1cc(-c2cnc3ccc(N(CCNC)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: ZNKBNXVWLPQHKJ-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 = 4.266 nM (pChEMBL 8.369999885559082)
Descriptors: MW 432.53, ALogP 3.89, HBA 8, HBD 1, PSA 77.33, QED 0.43
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCO)c3)nc2c1
InChIKey: CQDXYQFRLSRPQH-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 = 7.413 nM (pChEMBL 8.130000114440918)
Descriptors: MW 448.53, ALogP 2.86, HBA 9, HBD 2, PSA 97.56, QED 0.38
Compound (SMILES): COc1cc(OC)cc(N(CCCNS(=O)(=O)N(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HONWIFHKRIBHLZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 36.31 nM (pChEMBL 7.440000057220459)
Descriptors: MW 525.64, ALogP 2.97, HBA 9, HBD 1, PSA 114.71, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@@H]1CO[C@H]2[C@@H]1OC[C@@H]2OC
InChIKey: VENHPOQTVRCHJV-JXBRRONGSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 492.36, ALogP 4.5, HBA 8, HBD 1, PSA 83.96, QED 0.52
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3ccccn3)c2c(=O)n1-c1ccccc1
InChIKey: RYAQYDFEDXGXQC-FQEVSTJZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition Assays: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110δ/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 μg/mL). Reactions are initiated by the addition of ATP containing 10 μCi of γ-32P-ATP to a final concentration of 10 or 100 μM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 μL 1N HCl followed by 160 μL CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 525.57, ALogP 3.9, HBA 8, HBD 2, PSA 120.2, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ncccc2OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IHZFSYQVOKXLQL-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 = 34.67 nM (pChEMBL 7.460000038146973)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): COc1ccc(NC(=O)C2=C(c3ccc(C)cc3)C[C@](c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)NC2=O)cc1
InChIKey: FBBPRPJENPWDPL-LJAQVGFWSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: MGAT LCMS Assay: The MGAT enzyme reactions were performed in CORNING Falcon 96-well Polypropylene plates, in a total volume of 60 uL of 50 mM Potassium Phosphate buffer pH 7.4, containing a final concentration of 100 uM 2-oleoylglycerol, 15 uM oleoyl-Coenzyme A and 0.0013 ug/uL Human or Mouse MGAT-2 or 0.0026 ug/uL Rat recombinant MGAT-2 membranes expressed in Sf9 cells. Assay plates were run through a fully automated robotics system and shaken for 5 seconds every minute for a total 10 minutes. The reactions were then quenched with 120 uL of ice cold methanol containing 1 ug/mL 1,2-distearoyl-rac-glycerol as the internal standard. Plates were shaken for 2 minutes and spun down to remove protein precipitation. After the spin, samples were transferred to LC/MS compatible PCR plates. For LC/MS analysis, a ThermoFisher Surveyor pump, utilizing a Waters Symmetry C8, 50x2.1 mm column, was used for the chromatography of enzyme products.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 606.56, ALogP 7.09, HBA 4, HBD 2, PSA 76.66, QED 0.15
Compound (SMILES): COc1cc(O)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ZXPUNZSPQJIHJB-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 = 2.188 nM (pChEMBL 8.65999984741211)
Descriptors: MW 432.53, ALogP 3.88, HBA 8, HBD 2, PSA 88.33, QED 0.44
Compound (SMILES): CCN(C)Cc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PVNKKQPQLLGLMA-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.59, ALogP 5.04, HBA 7, HBD 0, PSA 59.31, QED 0.35
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(N)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PFFKWQNVRNBIGB-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 = 5.623 nM (pChEMBL 8.25)
Descriptors: MW 487.61, ALogP 3.61, HBA 9, HBD 1, PSA 94.56, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1.Cl
InChIKey: NDXCOBYSTJUJJD-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 = 2.754 nM (pChEMBL 8.5600004196167)
Descriptors: MW 474.61, ALogP 5.23, HBA 8, HBD 1, PSA 77.33, QED 0.34
Compound (SMILES): Cc1ccc(OCCNc2nc(Nc3cc(C)[nH]n3)cc(C)c2C#N)cn1
InChIKey: BOWYXGHFMQMXPT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Yes (SINGLE PROTEIN), Homo sapiens
UniProt: P07947
Assay: Inhibition of YES (unknown origin)
Measurement: Ki = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 363.43, ALogP 3.23, HBA 7, HBD 3, PSA 111.54, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CCNC[Si](C)(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: JMKXJKVYUUVONH-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 = 6.026 nM (pChEMBL 8.220000267028809)
Descriptors: MW 490.68
Compound (SMILES): COC(=N)c1nc2ccc3ncnc(Nc4ccc(OC)cc4F)c3c2s1
InChIKey: RYBNARZBIXTFJS-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of CLK2 (unknown origin)
Measurement: IC50 = 32.5 nM (pChEMBL 7.489999771118164)
Descriptors: MW 383.41, ALogP 4.1, HBA 8, HBD 2, PSA 93.01, QED 0.41
Compound (SMILES): Cc1ncccc1-n1c([C@H](C)Nc2nc(N)nc(N)c2C#N)nc2cccc(Cl)c2c1=O
InChIKey: MODOHQQWQXQEQB-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human full length PI3K p110gamma using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 447.89, ALogP 2.74, HBA 10, HBD 3, PSA 161.42, QED 0.43
Compound (SMILES): CCOc1ccnc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)n1
InChIKey: PRVGMAOUBRLMGU-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 = 19.05 nM (pChEMBL 7.71999979019165)
Descriptors: MW 521.58, ALogP 4.43, HBA 10, HBD 0, PSA 100.31, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(O)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JMBVTEKOAZJGIC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.122 nM (pChEMBL 8.949999809265137)
Descriptors: MW 511.54, ALogP 3.92, HBA 10, HBD 2, PSA 127.52, QED 0.32
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccn(C)c(=O)c1
InChIKey: JVGDBVAGMMZAGB-YKSBVNFPSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 expressed in microsomes using FCA as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 503.59, ALogP 4.56, HBA 7, HBD 0, PSA 55.95, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4cc5n(c4n3)C3(CCCCC3)CNC5=O)nc2)CC1
InChIKey: PDGKHKMBHVFCMG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human CDK4/cyclinD1
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 446.56, ALogP 2.72, HBA 8, HBD 2, PSA 91.21, QED 0.64
Compound (SMILES): COc1cc(OC)c(F)c(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1F
InChIKey: GLLVJFAKHOOPKT-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 = 2.754 nM (pChEMBL 8.5600004196167)
Descriptors: MW 536.51, ALogP 5.01, HBA 8, HBD 1, PSA 77.33, QED 0.23
Compound (SMILES): O=C(Nc1ccc(F)cc1)N1N=C(c2ccncc2)CC1c1ccc(F)cc1
InChIKey: RDQXNTXNNZITKD-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1I (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0X4
Assay: Inhibition of human T-type calcium channel Cav3.3 expressed in CHO cells assessed as inhibition of calcium tail current at -90 mV holding potential measured after 150 secs by QPatch assay
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 378.38, ALogP 4.74, HBA 3, HBD 1, PSA 57.59, QED 0.72
Compound (SMILES): COC/C(CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1)=N/O
InChIKey: YIDCCLXYFLNYHA-OGLMXYFKSA-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 = 47.86 nM (pChEMBL 7.320000171661377)
Descriptors: MW 462.51, ALogP 3.66, HBA 10, HBD 1, PSA 107.12, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: MMGNRRUXETXMDE-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 = 4.266 nM (pChEMBL 8.369999885559082)
Descriptors: MW 447.54, ALogP 4.61, HBA 8, HBD 1, PSA 85.53, QED 0.4
Compound (SMILES): Cc1ccc(CN2CC[C@@H](N3CC[C@@H](c4ccc(O)cc4)[C@H](F)C3)C2=O)cc1
InChIKey: UNVYDSCXINFREZ-BHDDXSALSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using BFC/BZR as substrate
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 382.48, ALogP 3.63, HBA 3, HBD 1, PSA 43.78, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: WPAMXPNNWJGKNP-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 = 8.128 nM (pChEMBL 8.09000015258789)
Descriptors: MW 449.51, ALogP 3.02, HBA 9, HBD 2, PSA 105.76, QED 0.38
Compound (SMILES): COc1cc(OC)cc(N(CC2CCN(C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BXMUZNHPFQUNSZ-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 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 472.59, ALogP 4.53, HBA 8, HBD 0, PSA 68.54, QED 0.39
Compound (SMILES): C[C@@H](c1nc2ccc(N3CCC[C@@H](C(=O)N4CCCC4)C3)nc2[nH]1)n1cc(Cl)cn1
InChIKey: NOSUIOGIJKVTAO-LSDHHAIUSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: DGAT2 Cell-Based Assay: For evaluation of the effects of DGAT2 inhibitors in a cell-based setting, cryopreserved human hepatocytes (Lot QOC, Celsis, Chicago, Ill.) were thawed and plated onto type I collagen-coated plates according to the manufacturer's instructions. After 24 hours overnight recovery period, the cells were overlayed with media containing 250 ug/ml Matrigel (BD Biosciences, San Jose, Calif.). The following day, media was aspirated and replaced with serum-free Williams Media E (Life Technologies, Grand Island, N.Y.) containing 400 uM sodium dodecanoate (Sigma-Aldrich, St. Louis, Mo.). Forty minutes later, DGAT2 inhibitors (prepared as 100× stocks in 25% DMSO, 75% Williams' Media E) were added to the desired final concentration. All wells contained a selective DGAT1 inhibitor (Example 3, WO2009016462) at a concentration (3 uM) that completely suppressed endogenous DGAT1 activity. After a 20 minute preincubation, 0.2 uCi [1,3-14C]-glycerol (American Radio Chemicals, St. Louis, Mo.) was added to each well and mixed by gentle pipetting prior to a 3 hour incubation. At this point, media was aspirated and the cells were lysed in isopropyl alcohol:tetrahydrofuran (9:1) prior to centrifugation at 3000 rpm for 5 minutes. Radiolabeled lipids were resolved using a 2-solvent system by thin layer chromatography using standard technique (solvent 1 contained ethyl acetate: isopropyl alcohol: chloroform:methanol:0.25% potassium chloride in water (100:100:100:40.2:36.1, v/v/v/v) and solvent 2 contained hexane: diethyl ether: acetic acid (70:27:3, v/v/v)). After separation, radiolabeled lipids were visualized using a Molecular Dynamics' PhosphorImager system. The half maximal inhibitory concentrations (IC50 values) were determined using Graph Pad Prism (GraphPad Software, Inc., La Jolla, Calif.).
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 427.94, ALogP 3.26, HBA 6, HBD 1, PSA 82.94, QED 0.69
Compound (SMILES): CCn1cc(-c2cnc3ccc(N(CCNC)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: ZNKBNXVWLPQHKJ-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 = 14.45 nM (pChEMBL 7.840000152587891)
Descriptors: MW 432.53, ALogP 3.89, HBA 8, HBD 1, PSA 77.33, QED 0.43
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCO)c3)nc2c1
InChIKey: CQDXYQFRLSRPQH-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 = 46.77 nM (pChEMBL 7.329999923706055)
Descriptors: MW 448.53, ALogP 2.86, HBA 9, HBD 2, PSA 97.56, QED 0.38
Compound (SMILES): COc1cc(OC)cc(N(CCCNS(=O)(=O)N(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HONWIFHKRIBHLZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.64, ALogP 2.97, HBA 9, HBD 1, PSA 114.71, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@@H]1CO[C@H]2[C@@H]1OC[C@@H]2OC
InChIKey: VENHPOQTVRCHJV-JXBRRONGSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
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 492.36, ALogP 4.5, HBA 8, HBD 1, PSA 83.96, QED 0.52