lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C4CC4)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: CJYGTSPFGMKIEK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR Exon 19 Deletion and Exon 20 T790M Concurrent Mutations: A compound's ability in selectively inhibiting EGFR exon 19 deletion and T790M concurrent mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR exon 19 deletion and T790M mutation. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR E746-A750 deletion and T790M Mutation, was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 19 deletion and T790M mutations. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR E746-A750 deletion and T790M Mutation virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR E746-A750 deletion and T790M Mutation (named Ba/F3-EGFR-Del/T790M) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-EGFR-Del/T790M cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 611.75, ALogP 5.87, HBA 10, HBD 2, PSA 113.85, QED 0.14
Compound (SMILES): C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1n1ccc2cnc3[nH]ccc3c21
InChIKey: UQVAOELSLJXOMB-DOMZBBRYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 321.38, ALogP 2.84, HBA 4, HBD 1, PSA 77.71, QED 0.79
Compound (SMILES): N=C(N)Nc1ccc(Oc2ccc(S(=O)(=O)CC3CS3)cc2)cc1
InChIKey: BZKOBLHHRSTMHO-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of MMP8 (unknown origin) assessed as inhibition constant
Measurement: Ki = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 363.46, ALogP 2.67, HBA 5, HBD 3, PSA 105.27, QED 0.41
Compound (SMILES): COCCCOc1cc2c(cc1OC)-c1cc(=O)c(C(=O)O)cn1[C@H](C(C)(C)C)CO2
InChIKey: PQMAMDUBYCMNAT-NRFANRHFSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 431.49, ALogP 3.62, HBA 7, HBD 1, PSA 96.22, QED 0.67
Compound (SMILES): Cc1nc2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc2n1C(C)C
InChIKey: NOWVRPHFPYFSDG-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR del (746 to 750) mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 438.52, ALogP 3.06, HBA 10, HBD 1, PSA 120.48, QED 0.49
Compound (SMILES): CC(C)c1nn(C(C)C)c2cc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)ncc12
InChIKey: WGQWOAUHLRBBJE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant autophosphorylation in human NCI-H1975 cells harboring harboring EGFR L858R/T790M double mutant preincubated for 60 mins followed by EGF stimulation and measured after 8 mins by SULFO-TAG based electrochemiluminescent assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 466.57, ALogP 3.87, HBA 10, HBD 1, PSA 120.48, QED 0.44
Compound (SMILES): C[C@@H]1CN(c2nc3ccc(Cl)cc3s2)CCN1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: KPLTXOWOJNWKCJ-CQSZACIVSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 480.42, ALogP 4.82, HBA 6, HBD 1, PSA 65.9, QED 0.52
Compound (SMILES): O=C1CC2Cc3ccsc3C2=NN1CCCCCCCN1CCN(Cc2cccc3c2ccn3S(=O)(=O)c2ccccc2)CC1
InChIKey: UHZOUSUGNFTACG-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured for 5 mins by Ellman's spectrophotometric method
Measurement: IC50 = 7180 nM (pChEMBL 5.139999866485596)
Descriptors: MW 643.88, ALogP 5.82, HBA 8, HBD 0, PSA 78.22, QED 0.18
Compound (SMILES): O=C(NO)c1cn(C2CCN(C(=O)Cc3ccc4ccccc4c3)CC2)nn1
InChIKey: VDICYJQVOFOYHC-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 379.42, ALogP 1.96, HBA 6, HBD 2, PSA 100.35, QED 0.53
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@]1(C)Cc2c([nH]c3ccccc23)CN([C@@H](CCCCN)C(=O)N[C@H](C(N)=O)[C@@H](C)O)C1=O
InChIKey: TVDHJWHHMJAOCK-QOSLDAFVSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Inhibition of human somatostatin receptor type 4
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 647.78, ALogP 0.52, HBA 7, HBD 7, PSA 212.74, QED 0.12
Compound (SMILES): C[C@H]1CCC[C@H]1n1c(=O)ccc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: ZUVPRDWNBVOFCM-XJKSGUPXSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: CDK2/Cyclin E1 Mobility Shift Assay: The purpose of the CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2) (SEQ ID NO:1). (CPC Scientific, Sunnyvale, Calif.). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Wild-type full length CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Mat1 enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (± inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA, pH 7.5. The Ki value was determined from the fit of the data to the Morrison tight-binding competitive inhibition equation with the enzyme concentration as a variable.
Measurement: Ki = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 405.52, ALogP 1.99, HBA 7, HBD 1, PSA 97.19, QED 0.84
Compound (SMILES): CC1=CC(C)=[N+]2C1=C(c1ccc(OCCn3cc(CCCCOc4cc(C(=O)O)nc5c(C)c6nc(C(=O)O)cc(O)c6cc45)nn3)cc1)c1nc(C)cn1[B-]2(F)F
InChIKey: OZMINXGQAXYZSF-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Binding affinity to Nluc-fused human GPR35 expressed in CHO-K1 cells using furimazine as substrate incubated for 30 mins in presence of zaprinast followed by substrate addition by BERT-based equilibrium binding assay
Measurement: Kd = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 790.59
Compound (SMILES): CC(=O)C1CCN(CCCOc2ccc3c(c2)CC[C@@H]2[C@@H]3CC[C@]3(C)[C@@H](N4CCCC4)CC[C@@H]23)CC1
InChIKey: JZHDMAKZPRQFAR-KQLGDFJMSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from Sprague-Dawley rat brain membrane histamine H3 receptor assessed as inhibition constant incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 492.75, ALogP 6.08, HBA 4, HBD 0, PSA 32.78, QED 0.43
Compound (SMILES): CNCc1cc(F)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(OC)c1
InChIKey: GUUQXMDBAHSFGF-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Binding affinity to recombinant human HPK1 (1 to 346 residues) expressed sf9 cells incubated for 1 hr by LanthaScreen assay
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 366.4, ALogP 2.89, HBA 6, HBD 2, PSA 80.65, QED 0.57
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@@H](Cc2ccccc2)NC(=O)c2ccncc2)CC1
InChIKey: JEJVZDGRLIYMOS-KAYWLYCHSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 499.62, ALogP 2.49, HBA 7, HBD 2, PSA 101.72, QED 0.42
Compound (SMILES): COc1cc(/C=C2\SC(=O)N(CCNC(=O)Nc3c(C)n(C)n(-c4ccccc4)c3=O)C2=O)cc(OC)c1OC
InChIKey: FDSDNMJXILQXBF-QNGOZBTKSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) by ELISA assay
Measurement: IC50 = 475 nM (pChEMBL 6.320000171661377)
Descriptors: MW 567.62, ALogP 3.37, HBA 10, HBD 2, PSA 133.13, QED 0.38
Compound (SMILES): COc1ccc(S(=O)(=O)N(Cc2ccccc2)c2c(C(=O)NO)ccc3c(C(C)(C)C)cccc23)cc1
InChIKey: FOTKISDMFBTXGP-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of TACE (unknown origin)
Measurement: IC50 = 401 nM (pChEMBL 6.400000095367432)
Descriptors: MW 518.64, ALogP 5.66, HBA 5, HBD 2, PSA 95.94, QED 0.24
Compound (SMILES): Cn1c(CCCN2CCN(c3cccc(Cl)c3Cl)CC2)nc(-c2ccccc2)c1C(=O)NCc1ccccc1
InChIKey: RDAMHUJTGOWZOX-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human D2 receptor expressed in HEK293T cells assessed as beta-arrestin recruitment preincubated for 10 mins with coelenterazine followed by compound addition and measured after 10 mins by BRET assay
Measurement: EC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 562.55, ALogP 6.08, HBA 5, HBD 1, PSA 53.4, QED 0.27
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)c(CC(F)F)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: GUFBYMCWKSZUBS-IIBYNOLFSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 485.56, ALogP 1.91, HBA 8, HBD 2, PSA 117.42, QED 0.64
Compound (SMILES): Cc1onc(-c2ccccc2)c1/C=C/c1ccc(CNC(=O)C(C)S)cc1
InChIKey: DGOYOCWNRBRVGP-OUKQBFOZSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 378.5, ALogP 4.75, HBA 4, HBD 2, PSA 55.13, QED 0.61
Compound (SMILES): C#Cc1cccc(Nc2ncnc3cc(OC)c(OCCCN4CCOCC4)cc23)c1
InChIKey: WBKHQQZRHCECKK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR L858R/T790M mutant using 5-FAM-EEPLYWSFPAKKKCONH2 as substrate incubated for 30 mins in presence of ATP
Measurement: IC50 = 208.9 nM (pChEMBL 6.679999828338623)
Descriptors: MW 418.5, ALogP 3.46, HBA 7, HBD 1, PSA 68.74, QED 0.44
Compound (SMILES): CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)SCCCCCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2c(sc(C)c2C)-n2c(C)nnc21
InChIKey: FNDFWBANYDEWBA-MVIMOGLESA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to BRD3 BD2 domain (unknown origin)
Measurement: Kd = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 958.68, ALogP 7.2, HBA 13, HBD 4, PSA 183.8, QED 0.07
Compound (SMILES): O=C(CCCCCCNCc1cc2ccccc2[nH]1)NO
InChIKey: KZPHOMXAZIKWEU-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli BL21 (DE3) cells by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 289.38, ALogP 2.71, HBA 3, HBD 4, PSA 77.15, QED 0.33
Compound (SMILES): CCN(CCCCCCCCCCCCn1cc(C=O)c2cc(OC)ccc21)Cc1cccc(O)c1
InChIKey: OESTWNDKVZPZBM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 492.7, ALogP 7.59, HBA 5, HBD 1, PSA 54.7, QED 0.15
Compound (SMILES): Cn1ncc2cc(CN3CCO[C@H](COc4ccc(F)c(F)c4)C3)ccc21
InChIKey: JAKIOOTWQGBKAJ-KRWDZBQOSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 28.18 nM (pChEMBL 7.550000190734863)
Descriptors: MW 373.4, ALogP 3.13, HBA 5, HBD 0, PSA 39.52, QED 0.69
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C12CCN(CC1)CC2)c1ncc(-c2cc3ccccc3nc2OC)o1
InChIKey: NBVPHNBDESFHFB-VWLOTQADSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG potassium channel incubated for 4 hrs by fluorescence polarization assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 518.66, ALogP 5.47, HBA 7, HBD 1, PSA 97.56, QED 0.32
Compound (SMILES): CC[C@H](C)n1nc(N2CC(C(C)(C)O)C2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: RDWYRIOEHIKPRE-INIZCTEOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant autophosphorylation in human NCI-H1975 cells harboring harboring EGFR L858R/T790M double mutant preincubated for 60 mins followed by EGF stimulation and measured after 8 mins by SULFO-TAG based electrochemiluminescent assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 551.68, ALogP 3.35, HBA 12, HBD 2, PSA 143.95, QED 0.32
Compound (SMILES): Cc1n[nH]c2cc(N(C(=O)NCCCn3cncc3C)C3CCCCC3)ccc12
InChIKey: DWKOIVNSZJZOOM-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Mus musculus
UniProt: Q9CYK2
Assay: Inhibition of mouse glutaminyl cyclase
Measurement: IC50 = 34.2 nM (pChEMBL 7.46999979019165)
Descriptors: MW 394.52, ALogP 4.32, HBA 4, HBD 2, PSA 78.84, QED 0.61
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc([N+](=O)[O-])c4)n3)cc2C(F)(F)F)CC1
InChIKey: QZAFKCISRNOJGA-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human Cdk2/Cyclin A using Myelin basic protein as substrate by ATP competitive assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 458.44, ALogP 4.57, HBA 7, HBD 1, PSA 87.43, QED 0.44
Compound (SMILES): COc1cccc(/C=C/C(=O)NC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)c1
InChIKey: YQXARSVRDPJIEQ-RCJYHZQCSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 518.56, ALogP 4.43, HBA 4, HBD 2, PSA 84.5, QED 0.39
Compound (SMILES): O=C1c2ccccc2C(=O)N1c1nc2cc([N+](=O)[O-])ccc2n1Cc1ccc(-c2ccccc2)cc1
InChIKey: FMXPLCOPRJODRZ-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid lipoxygenase ALOX15 (SINGLE PROTEIN), Homo sapiens
UniProt: P16050
Assay: Inhibition of 15-LOX (unknown origin)
Measurement: IC50 = 1020 nM (pChEMBL 5.989999771118164)
Descriptors: MW 474.48, ALogP 5.46, HBA 6, HBD 0, PSA 98.34, QED 0.19
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccccc3F)cc2)nc2cnccc12)C(N)=O
InChIKey: UAFHHPALEOOBTA-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 = 3070 nM (pChEMBL 5.510000228881836)
Descriptors: MW 425.47, ALogP 4.65, HBA 5, HBD 2, PSA 104.69, QED 0.47
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(C)(C)O)cc2OC)c2cc[nH]c2c1=O
InChIKey: GVJYOLRRZZUUOE-AATRIKPKSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged CECR2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 352.43, ALogP 3.81, HBA 4, HBD 2, PSA 67.25, QED 0.69
Compound (SMILES): COc1cccc(Cl)c1NCc1cc(=O)n2nc(-c3ccccc3)nc2[nH]1
InChIKey: PEPOAHRJJMETTF-UHFFFAOYSA-N
Target: Fatty acid-binding protein, adipocyte (SINGLE PROTEIN), Homo sapiens
UniProt: P15090
Assay: Displacement of BODIPY 500/510 C4 from human FABP4 expressed in Escherichia coli incubated for 30 mins by FP assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 381.82, ALogP 3.36, HBA 6, HBD 2, PSA 84.31, QED 0.55
Compound (SMILES): COc1ccc(-c2ccc(Oc3ccccc3C(C)(C)C)c(NC(=O)Nc3ccccc3F)c2)cc1C(=O)O
InChIKey: XAJOXNWLUKPUDW-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 528.58, ALogP 7.93, HBA 4, HBD 3, PSA 96.89, QED 0.23
Compound (SMILES): COc1ccc(-c2ccc3nc(C)c(-c4cnc(N)c(C(F)(F)F)c4)n3n2)cc1OC
InChIKey: ZMTTVTGSKOFZGH-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin)
Measurement: IC50 = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 429.4, ALogP 4.38, HBA 7, HBD 1, PSA 87.56, QED 0.52
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ccc(F)cc1
InChIKey: ITGWQDKBZORLFI-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Antagonist activity at glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as inhibition of dexamethasone-induced transactivation of receptor incubated for 18 hrs by firefly luciferase assay
Measurement: IC50 = 14220 nM (pChEMBL 4.849999904632568)
Descriptors: MW 488.97, ALogP 5.19, HBA 4, HBD 1, PSA 75.71, QED 0.54
Compound (SMILES): COCCCC(=O)NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: RCOSLDFGEVGMJF-VZYDHVRKSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 497.04, ALogP 3.65, HBA 6, HBD 1, PSA 76.46, QED 0.41
Compound (SMILES): CC(C)n1cc(C(=O)NC2COC2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: ZKEOBSJWSQXRIH-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR del (746 to 750) mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 522.59, ALogP 2.48, HBA 11, HBD 2, PSA 145.92, QED 0.36
Compound (SMILES): NS(=O)(=O)c1ccc(N2N=C(c3ccc(O)cc3)CC2c2cccs2)cc1
InChIKey: IPSZZGQBFIICSX-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 399.5, ALogP 3.46, HBA 6, HBD 2, PSA 95.99, QED 0.7
Compound (SMILES): Cn1c2ccccc2c2cc[n+](-c3ccc(I)cc3)cc21
InChIKey: PFXJDWFVKKAJGD-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin) incubated for 40 mins by Ellman's method
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 385.23, ALogP 4.21, HBA 1, HBD 0, PSA 8.81, QED 0.34
Compound (SMILES): O=[N+]([O-])c1ccccc1-n1cc(COc2cccc3cnc(Nc4cccc(Cl)c4)nc23)nn1
InChIKey: XYFHSCKRPLMJIO-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of human CLK4
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 473.88, ALogP 5.09, HBA 9, HBD 1, PSA 120.89, QED 0.26
Compound (SMILES): O=C(c1cccc(-c2n[nH]c3ncc(Cc4cc(F)ccc4F)cc23)c1)N1CCCC(O)C1
InChIKey: JRLOPMVTMMPZMV-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TRKC (unknown origin) using TK as substrate in presence of ATP incubated for 40 mins by HTRF KinEASE assay
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 448.47, ALogP 4.09, HBA 4, HBD 2, PSA 82.11, QED 0.49
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)C1CC1
InChIKey: ZQLQFWNFWSRBRS-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Antagonist activity at glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as inhibition of dexamethasone-induced transactivation of receptor incubated for 18 hrs by firefly luciferase assay
Measurement: IC50 = 9210 nM (pChEMBL 5.039999961853027)
Descriptors: MW 434.95, ALogP 4.15, HBA 4, HBD 1, PSA 75.71, QED 0.77
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(C)c2)c2cc(C)[nH]c2c1=O
InChIKey: WHKOQEHRVJBOCH-SNAWJCMRSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged TAF1 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 405.5, ALogP 3.66, HBA 4, HBD 1, PSA 67.33, QED 0.67
Compound (SMILES): O=C1Nc2cc(S(=O)(=O)Cc3c(Cl)cccc3Cl)ccc2S/C1=C\c1ccc(O)c([N+](=O)[O-])c1
InChIKey: DOMBZVXKSRQDOJ-NKVSQWTQSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 537.4, ALogP 5.67, HBA 7, HBD 2, PSA 126.61, QED 0.24
Compound (SMILES): CC(=O)c1c(C)c2cnc(NC3CCN(S(C)(=O)=O)CC3)nc2n(C2CCCC2)c1=O
InChIKey: BMHDAQPPVLYLRR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Binding affinity to CDK2 (unknown origin) extracted from insect cells assessed as inhibition constant
Measurement: Ki = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 447.56, ALogP 2.25, HBA 8, HBD 1, PSA 114.26, QED 0.7
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc3c(ncn3C)c2N2CC[C@@H](N)C2)n1
InChIKey: ORQCQXMGDYAIOI-CQSZACIVSA-N
Target: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13131
Assay: Inhibition of PRKAA1 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 202 nM (pChEMBL 6.699999809265137)
Descriptors: MW 461.5, ALogP 2.97, HBA 8, HBD 2, PSA 111.19, QED 0.47
Compound (SMILES): c1ccc2c(c1)[nH]c1cnc3c4ccncc4[nH]c3c12
InChIKey: RZXWKGHDRQNABH-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16445
Assay: Binding affinity to human recombinant GABAA alpha6 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 258.28, ALogP 3.75, HBA 2, HBD 2, PSA 57.36, QED 0.44
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccnc(N5CCOCC5)c4)c3c2)[C@@H](C)n2nnnc2N1C
InChIKey: SLIDWZKKXCTTPU-OAHLLOKOSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 expressed in HEK293 cells assessed as reduction in pS1292 phosphorylation incubated for 2 hrs by MSD analysis
Measurement: IC50 = 20.9 nM (pChEMBL 7.679999828338623)
Descriptors: MW 486.54, ALogP 2.37, HBA 10, HBD 2, PSA 129.98, QED 0.45
Compound (SMILES): O=C(Nc1nnn[nH]1)c1cc(Cl)c(Oc2ncccc2C(=O)N2CCN(C3CC3)c3ccccc32)cc1Cl
InChIKey: KVASBUNZQLUXCB-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 551.39, ALogP 4.58, HBA 8, HBD 2, PSA 129.23, QED 0.36
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C4CC4)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: CJYGTSPFGMKIEK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: HER2 Exon 20 YVMA Insertion Mutation: A compound's ability in selectively inhibiting Her2 exon 20 YVMA insertion mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with Her2 Exon20 YVMA insertions. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR exon 20 insertions YVMA (A775_G776ins YVMA), was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 20 insertions. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR Exon20 virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing Her2 Exon20 YVMA insertions (named Ba/F3-Her2 Exon20 YVMA) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-Her2 Exon20 YVMA cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 611.75, ALogP 5.87, HBA 10, HBD 2, PSA 113.85, QED 0.14
Compound (SMILES): C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1n1ccc2cnc3[nH]ccc3c21
InChIKey: UQVAOELSLJXOMB-DOMZBBRYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 321.38, ALogP 2.84, HBA 4, HBD 1, PSA 77.71, QED 0.79
Compound (SMILES): N=C(N)Nc1ccc(Oc2ccc(S(=O)(=O)CC3CS3)cc2)cc1
InChIKey: BZKOBLHHRSTMHO-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Enzyme Inhibition Assay: Human recombinant active MMP-2 and MMP-7, and the catalytic domains of MMP-3 and MMP-14/MT1-MMP were purchased from EMD Chemicals, Inc. (San Diego, Calif., USA); human recombinant catalytic domains of MMP-1, MMP-8, and MMP-9 were purchased from Enzo Life Sciences, Inc. (Farmingdale, N.Y., USA); human recombinant active ADAM9 and ADAM10 were purchased from R&D Systems (Minneapolis, Minn., USA). Fluorogenic substrates MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 (for MMP-2, MMP-7, MMP-9 and MMP-14) and MOCAc-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH2 (for MMP-3) were purchased from Peptides International (Louisville, Ky., USA); Mca-KPLGL-Dpa-AR-NH2 (for MMP-1, MMP-8 and ADAM10) and Mca-PLAQAV-Dpa-RSSSR-NH2 (for ADAM9) were purchased from R&D Systems (Minneapolis, Minn., USA). The Km values for MMP-2, MMP-9 and MMP-14 were the same as previously reported by Gooyit et al. ((2013) J. Med. Chem. 56(20):8139-8150). Inhibitor stock solutions (10 mM) were prepared freshly in DMSO before enzyme inhibition assays. We followed the same methodology for enzyme inhibition studies as reported before by Page-McCaw et al. ((2007) Nat Rev Mol Cell Biol 8(3):221-233). Enzyme inhibition studies were carried out using a Cary Eclipse fluorescence spectrophotometer (Varian, Walnut Creek, Calif., USA). Compound 1 was stable in the buffers used in the kinetic assays.
Measurement: Ki = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 363.46, ALogP 2.67, HBA 5, HBD 3, PSA 105.27, QED 0.41
Compound (SMILES): COCCCOc1cc2c(cc1OC)-c1cc(=O)c(C(=O)O)cn1[C@H](C(C)(C)C)CO2
InChIKey: PQMAMDUBYCMNAT-NRFANRHFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 431.49, ALogP 3.62, HBA 7, HBD 1, PSA 96.22, QED 0.67
Compound (SMILES): Cc1nc2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc2n1C(C)C
InChIKey: NOWVRPHFPYFSDG-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type human EGFR assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 438.52, ALogP 3.06, HBA 10, HBD 1, PSA 120.48, QED 0.49
Compound (SMILES): CC(C)c1nn(C(C)C)c2cc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)ncc12
InChIKey: WGQWOAUHLRBBJE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR T790M/L858R double mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as peptide substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 466.57, ALogP 3.87, HBA 10, HBD 1, PSA 120.48, QED 0.44
Compound (SMILES): C[C@@H]1CN(c2nc3ccc(Cl)cc3s2)CCN1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: KPLTXOWOJNWKCJ-CQSZACIVSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPAR-alpha ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 480.42, ALogP 4.82, HBA 6, HBD 1, PSA 65.9, QED 0.52
Compound (SMILES): O=C(NO)c1cn(C2CCN(C(=O)Cc3ccc4ccccc4c3)CC2)nn1
InChIKey: VDICYJQVOFOYHC-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 379.42, ALogP 1.96, HBA 6, HBD 2, PSA 100.35, QED 0.53
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@]1(C)Cc2c([nH]c3ccccc23)CN([C@@H](CCCCN)C(=O)N[C@H](C(N)=O)[C@@H](C)O)C1=O
InChIKey: TVDHJWHHMJAOCK-QOSLDAFVSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Inhibition of human somatostatin receptor type 5
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 647.78, ALogP 0.52, HBA 7, HBD 7, PSA 212.74, QED 0.12
Compound (SMILES): C[C@H]1CCC[C@H]1n1c(=O)ccc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: ZUVPRDWNBVOFCM-XJKSGUPXSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 0.13 nM (pChEMBL 9.890000343322754)
Descriptors: MW 405.52, ALogP 1.99, HBA 7, HBD 1, PSA 97.19, QED 0.84
Compound (SMILES): CNCc1cc(F)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(OC)c1
InChIKey: GUUQXMDBAHSFGF-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of human HPK1 in human Jurkat cells assessed as reduction in SLP76 phosphorylation incubated for 1 hr by HTRF assay
Measurement: IC50 = 219 nM (pChEMBL 6.659999847412109)
Descriptors: MW 366.4, ALogP 2.89, HBA 6, HBD 2, PSA 80.65, QED 0.57
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)c(CC(F)F)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: GUFBYMCWKSZUBS-IIBYNOLFSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: CDK2/Cyclin E1 Mobility Shift Assay : The purpose of the CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2) (SEQ ID NO:1). (CPC Scientific, Sunnyvale, Calif.). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Wild-type full length CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Mat1 enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (±inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA, pH 7.5. The Ki value was determined from the fit of the data to the Morrison tight-binding competitive inhibition equation with the enzyme concentration as a variable.
Measurement: Ki = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 485.56, ALogP 1.91, HBA 8, HBD 2, PSA 117.42, QED 0.64
Compound (SMILES): CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)SCCCCCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2c(sc(C)c2C)-n2c(C)nnc21
InChIKey: FNDFWBANYDEWBA-MVIMOGLESA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 BD1 domain (unknown origin)
Measurement: Kd = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 958.68, ALogP 7.2, HBA 13, HBD 4, PSA 183.8, QED 0.07
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc([N+](=O)[O-])c4)n3)cc2C(F)(F)F)CC1
InChIKey: QZAFKCISRNOJGA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Binding affinity to Mycobacterium tuberculosis partial length PknB (M1 to G279 residues) expressed in mammalian expression system by KdELECT kinase assay
Measurement: Kd = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 458.44, ALogP 4.57, HBA 7, HBD 1, PSA 87.43, QED 0.44
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccccc3F)cc2)nc2cnccc12)C(N)=O
InChIKey: UAFHHPALEOOBTA-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 425.47, ALogP 4.65, HBA 5, HBD 2, PSA 104.69, QED 0.47
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(C)(C)O)cc2OC)c2cc[nH]c2c1=O
InChIKey: GVJYOLRRZZUUOE-AATRIKPKSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged TAF1 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 352.43, ALogP 3.81, HBA 4, HBD 2, PSA 67.25, QED 0.69
Compound (SMILES): COc1ccc(-c2ccc(Oc3ccccc3C(C)(C)C)c(NC(=O)Nc3ccccc3F)c2)cc1C(=O)O
InChIKey: XAJOXNWLUKPUDW-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: IDO Kynurenine Assay: Human IDO1/HEK293 cells were seeded at 10,000 cells per 50 uL per well with RPMI/phenol red free media contains 10% FBS in a 384-well black wall clear bottom tissue culture plate (Matrix Technologies LLC) 125 nL of certain concentration of compound was then added to each well using ECHO liquid handling systems. The cells were incubated for 20 hours in 37° C. incubator with 5% CO2.The compound treatments were stopped by adding Trichloroacetic Acid (Sigma-Aldrich) to a final concentration at 0.2%. The cell plate was further incubated at 50° C. for 30 minute. The equal volume supernatant (20 uL) and 0.2% (w/v) Ehrlich reagent (4-dimethylaminobenzaldehyde, Sigma-Aldrich) in glacial acetic acid were mixed in a new clear bottom 384-well plate. This plate was then incubated at room temperature for 30 minute. The absorbance at 490 nm was measured on Envision plate reader.Compound IC50 values were calculated using the counts of 500 nM of a reference standard treatment as one hundred percent inhibition, and counts of no compound but DMSO treatment as zero percent inhibition.
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 528.58, ALogP 7.93, HBA 4, HBD 3, PSA 96.89, QED 0.23
Compound (SMILES): COCCCC(=O)NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: RCOSLDFGEVGMJF-VZYDHVRKSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Antagonist activity against recombinant human H1 receptor expressed in CHO cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 497.04, ALogP 3.65, HBA 6, HBD 1, PSA 76.46, QED 0.41
Compound (SMILES): CC(C)n1cc(C(=O)NC2COC2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: ZKEOBSJWSQXRIH-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type human EGFR assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 522.59, ALogP 2.48, HBA 11, HBD 2, PSA 145.92, QED 0.36
Compound (SMILES): O=C(c1cccc(-c2n[nH]c3ncc(Cc4cc(F)ccc4F)cc23)c1)N1CCCC(O)C1
InChIKey: JRLOPMVTMMPZMV-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) using TK as substrate in presence of ATP incubated for 30 mins by HTRF KinEASE assay
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 448.47, ALogP 4.09, HBA 4, HBD 2, PSA 82.11, QED 0.49
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(C)c2)c2cc(C)[nH]c2c1=O
InChIKey: WHKOQEHRVJBOCH-SNAWJCMRSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to ZsGreen fused-BRD9 (M1 to T597 residues) (unknown origin) expressed in human U2OS-C433 cells assessed as induction of protein bromodomain localization from chromatin by measuring formation of large nuclear puncta by fluorescence based assay
Measurement: EC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 405.5, ALogP 3.66, HBA 4, HBD 1, PSA 67.33, QED 0.67
Compound (SMILES): O=C1Nc2cc(S(=O)(=O)Cc3c(Cl)cccc3Cl)ccc2S/C1=C\c1ccc(O)c([N+](=O)[O-])c1
InChIKey: DOMBZVXKSRQDOJ-NKVSQWTQSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of recombinant human CLK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 537.4, ALogP 5.67, HBA 7, HBD 2, PSA 126.61, QED 0.24
Compound (SMILES): CC(=O)c1c(C)c2cnc(NC3CCN(S(C)(=O)=O)CC3)nc2n(C2CCCC2)c1=O
InChIKey: BMHDAQPPVLYLRR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Binding affinity to CDK4 (unknown origin) assessed as inhibition constant
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 447.56, ALogP 2.25, HBA 8, HBD 1, PSA 114.26, QED 0.7
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc3c(ncn3C)c2N2CC[C@@H](N)C2)n1
InChIKey: ORQCQXMGDYAIOI-CQSZACIVSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 461.5, ALogP 2.97, HBA 8, HBD 2, PSA 111.19, QED 0.47
Compound (SMILES): c1ccc2c(c1)[nH]c1cnc3c4ccncc4[nH]c3c12
InChIKey: RZXWKGHDRQNABH-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14867
Assay: Inhibition of GABAA alpha1 receptor (unknown origin)
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 258.28, ALogP 3.75, HBA 2, HBD 2, PSA 57.36, QED 0.44
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccnc(N5CCOCC5)c4)c3c2)[C@@H](C)n2nnnc2N1C
InChIKey: SLIDWZKKXCTTPU-OAHLLOKOSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in HEK293 cells assessed as reduction in pS1292 phosphorylation incubated for 2 hrs by MSD analysis
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 486.54, ALogP 2.37, HBA 10, HBD 2, PSA 129.98, QED 0.45
Compound (SMILES): C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1n1ccc2cnc3[nH]ccc3c21
InChIKey: UQVAOELSLJXOMB-DOMZBBRYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 0.46 nM (pChEMBL 9.34000015258789)
Descriptors: MW 321.38, ALogP 2.84, HBA 4, HBD 1, PSA 77.71, QED 0.79