lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1c2ccc(N(C)c3ccnc(Nc4ccc(C(=O)NCCCCCCC(=O)NO)cc4)n3)cc2nn1C
InChIKey: PSNSRJNHZPJVJH-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR-2 (unknown origin) after 40 mins by kinase-Glo assay
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 530.63, ALogP 4.37, HBA 9, HBD 4, PSA 137.3, QED 0.12
Compound (SMILES): Cc1cc(CC(=O)Nc2ccn(Cc3ccc(C#N)cn3)n2)ccc1OC(F)(F)F
InChIKey: GJKURPNQOJQXPQ-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of recombinant Cav1.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by KCl addition by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 1480 nM (pChEMBL 5.829999923706055)
Descriptors: MW 415.38, ALogP 3.59, HBA 6, HBD 1, PSA 92.83, QED 0.66
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Cc4ccc(C(=O)NO)s4)ccc3OCC)nc12
InChIKey: NGFDENLSEDFSFN-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human recombinant N-terminal GST-tagged HDAC6 expressed in baculovirus infected sf9 cells using fluorogenic HDAC substrate 3 after 30 mins by fluorescence assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 467.55, ALogP 3.45, HBA 8, HBD 3, PSA 122.13, QED 0.27
Compound (SMILES): CCn1cc(-c2cc(C(=O)OC)n(C)n2)c2ccccc21
InChIKey: MUXTUOACDPIOSX-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 catalytic domain preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 283.33, ALogP 2.85, HBA 5, HBD 0, PSA 49.05, QED 0.69
Compound (SMILES): O=S(=O)(NC1CCN(CC(O)COc2ccccc2-c2ccccc2)CC1)c1cccc(Cl)c1
InChIKey: JFHVZERFQKQSFW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in HEK293 or CHO-K1 cells after 1 hr by microbeta counting analysis
Measurement: Ki = 295 nM (pChEMBL 6.53000020980835)
Descriptors: MW 501.05, ALogP 4.19, HBA 5, HBD 2, PSA 78.87, QED 0.46
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCC2)NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: ZWTUZOQCWSYYNO-AGEXMYHWSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 888, ALogP -0.31, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): CCN(Cc1ccccc1)Cc1ccc(NC(=O)Cc2ccc(O)c(O)c2)cc1
InChIKey: NXGXSRJQERFLRS-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE using S-butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured up to 180 secs by spectrophotometric analysis
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 390.48, ALogP 4.3, HBA 4, HBD 3, PSA 72.8, QED 0.5
Compound (SMILES): CCCCOc1ccc(C2=N[C@@H](CO)[C@H](C)S2)cc1
InChIKey: VJHCELMTVAQBMD-FZMZJTMJSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]Ketanserin from 5-HT2A (unknown origin) receptor after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 279.41, ALogP 3.11, HBA 4, HBD 1, PSA 41.82, QED 0.81
Compound (SMILES): Cl.FCCOc1ccc(CCC2CCN(CCc3ccccc3Cl)CC2)cc1
InChIKey: QJGKZUYMJASPAX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]Dofetilide from human ERG expressed in HEK293 cells after 60 mins by scintillation spectrometry
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 389.94, ALogP 5.58, HBA 2, HBD 0, PSA 12.47, QED 0.56
Compound (SMILES): Cn1c(=O)n(CCN2CCN(c3ccc(C#N)cc3)CC2)c2nc(N)n3nc(-c4ccco4)nc3c21
InChIKey: RWGBSTYGWOSDSQ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Antagonist activity at rat A2A receptor assessed as reduction in CGS-21680-induced cAMP level pretreated for 15 mins followed by CGS-21680 addition measured after 30 mins by HTRF assay
Measurement: Ki = 1.15 nM (pChEMBL 8.9399995803833)
Descriptors: MW 484.52, ALogP 1.31, HBA 12, HBD 1, PSA 139.44, QED 0.39
Compound (SMILES): CCCC(=O)N(C)[C@H](C(=O)N1CCC[C@H]1C(=O)N(C)[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N(C)[C@H](C(=O)N(C)Cc1nccs1)C(C)C)C(C)C
InChIKey: XNASEKUWNLNRSN-LMUGUXCZSA-N
Target: Sterol O-acyltransferase 2 (SINGLE PROTEIN), Chlorocebus aethiops
UniProt: O77759
Assay: Inhibition of African green monkey SOAT2 expressed in CHO cell microsomal fractions assessed as reduction in neutral lipid synthesis incubated for 6 hrs using [1-14C]oleoyl-CoA by thin-layer chromatography
Measurement: IC50 = 9600 nM (pChEMBL 5.019999980926514)
Descriptors: MW 796.09, ALogP 4.46, HBA 8, HBD 1, PSA 143.54, QED 0.22
Compound (SMILES): N#Cc1ccnc(N2C(=O)CC[C@H]2C(=O)N(c2cncc(F)c2)C(C(=O)NC2CC(F)(F)C2)c2ccccc2Cl)c1
InChIKey: WIJZXSAJMHAVGX-XADRRFQNSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assay: A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 582.97, ALogP 4.32, HBA 6, HBD 1, PSA 119.29, QED 0.44
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CN)C(N)=O
InChIKey: GBWDHKBLRMDDCK-DKTXOJPGSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of PGPH activity of human 26S proteasome using Z-LLE-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 1323.6
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: SFAJGGFDBDWTMC-BAGYTPMASA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 632.67, ALogP 2.63, HBA 9, HBD 6, PSA 224.81, QED 0.04
Compound (SMILES): Cc1nn(C)c2nc(NNC(=O)Nc3cc(Cl)nc(OCC4CC4)c3)cc(C(C)C)c12
InChIKey: KATYKXXGQBFJLO-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95977
Assay: Displacement of [32P]S1P from recombinant human S1PR4 expressed in cell membranes pretreated for 30 mins followed by [32P]S1P addition measured after 60 mins by scintillation counting method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 443.94, ALogP 4.39, HBA 7, HBD 3, PSA 105.99, QED 0.37
Compound (SMILES): CCC(=C(c1ccc(OCCN2CCCCCC2)cc1)c1ccc(OCCN2CCCCCC2)cc1)c1cccc(C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)c1
InChIKey: SBODERJBBPEJRV-ASNOGBRRSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of PGPH activity of human 26S proteasome using Z-LLE-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1916.42
Compound (SMILES): COc1cc(NC(C(=O)c2c[nH]c3ccccc23)c2ccccc2)cc(OC)c1
InChIKey: RUOUETBOFZRKGX-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 386.45, ALogP 5.22, HBA 4, HBD 2, PSA 63.35, QED 0.43
Compound (SMILES): Cc1cc(-n2cc3c(n2)CN(C(=O)c2cc(C#N)ccc2-c2cccc(F)c2)C3)ccn1
InChIKey: YIXNGZTVLPLRHN-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent glycine transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y345
Assay: Inhibition of recombinant human GlyT2 expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.45, ALogP 4.41, HBA 5, HBD 0, PSA 74.81, QED 0.49
Compound (SMILES): C[C@@H]1SC(c2ccccc2O)=N[C@H]1Cc1c[nH]cn1
InChIKey: YSCNOWHLCXMNDZ-CABZTGNLSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor expressed in HEK cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 273.36, ALogP 2.61, HBA 4, HBD 2, PSA 61.27, QED 0.9
Compound (SMILES): CS(=O)(=O)N1CCN(Cc2cc3c(N4CCOCC4)nc(-c4cnc(N)nc4)cn3n2)CC1
InChIKey: XEBRAMSBPJUGET-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant full-length human N-terminal His6-tagged p110gamma expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate by HTRF assay
Measurement: Ki = 49.1 nM (pChEMBL 7.309999942779541)
Descriptors: MW 473.56, ALogP -0.32, HBA 11, HBD 1, PSA 135.08, QED 0.53
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(C(O)c4ccc(C(=O)NO)cc4)ccc3OCC)nc12
InChIKey: IUQUWTOVRNIGDN-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of full length human recombinant N-terminal GST-tagged PDE5A1 expressed in baculovirus infected sf9 cells using cGMP as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 477.52, ALogP 2.88, HBA 8, HBD 4, PSA 142.36, QED 0.23
Compound (SMILES): O=S(=O)(Oc1ccccc1Cl)C1CC2OC1C(c1ccc(/C=C/c3cc(O)cc(O)c3)cc1)=C2c1ccc(O)cc1
InChIKey: CQDCBCLWITTXGG-AATRIKPKSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Agonist activity at human ERbeta expressed in HEK293T cells after 24 hrs by ERE-based dual luciferase reporter gene assay
Measurement: EC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 589.07, ALogP 6.49, HBA 7, HBD 3, PSA 113.29, QED 0.17
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccccc2NC(=O)CO)n1
InChIKey: BQBNPQXFWWIVER-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 2070 nM (pChEMBL 5.679999828338623)
Descriptors: MW 498.97, ALogP 3.36, HBA 9, HBD 3, PSA 112.08, QED 0.43
Compound (SMILES): O=C(O)c1noc(-c2ccccc2)c1-c1cccc(-c2cccc(O)c2)c1
InChIKey: HDBQZCCNZOGXEE-UHFFFAOYSA-N
Target: Phosphotyrosine-protein phosphatase PTPB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P96830
Assay: Inhibition of Mycobacterium tuberculosis H37Rv His-tagged ptpB H94A mutant expressed in Escherichia coli BL21(DE3) using pNPP as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 357.37, ALogP 5.08, HBA 4, HBD 2, PSA 83.56, QED 0.53
Compound (SMILES): CCC(SC1=Nc2ccccc2C2=NC(C(C)CC)C(=O)N12)C(=O)Nc1ccccc1C
InChIKey: HTFJGDBBWXQQCN-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Stabilization of ALDH1A1 in human OV90 cells assessed as increase in melting temperature at 70 degC after 1 hr by CETSA
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 448.59, ALogP 5.15, HBA 5, HBD 1, PSA 74.13, QED 0.66
Compound (SMILES): O=S(=O)(c1ccc(F)cc1)N1CCCc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc21
InChIKey: VDGMDLWYOUANBX-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at GAL4-tagged human LXRbeta assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 = 223 nM (pChEMBL 6.650000095367432)
Descriptors: MW 457.37, ALogP 4.28, HBA 3, HBD 1, PSA 57.61, QED 0.7
Compound (SMILES): Cl.Cl.FCCOc1ccccc1CCN1CCN(CCc2ccccc2)CC1
InChIKey: ZMAVQUKGEDDCHL-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]Dofetilide from human ERG expressed in HEK293 cells after 60 mins by scintillation spectrometry
Measurement: IC50 = 5490 nM (pChEMBL 5.260000228881836)
Descriptors: MW 356.49, ALogP 3.44, HBA 3, HBD 0, PSA 15.71, QED 0.68
Compound (SMILES): NC(=O)c1ccc(-c2cn3c(-c4ccc(O)cc4)cnc3cn2)cc1
InChIKey: LKFLRBIQIXBCCO-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: Inhibition of GST-tagged MNK1 (37 to 341 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) using JH3 peptide as substrate preincubated for 10 mins followed by substrate and ATP addition measured after 60 mins
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 330.35, ALogP 2.87, HBA 5, HBD 2, PSA 93.51, QED 0.6
Compound (SMILES): COc1ccccc1CCN1CCC(CCc2ccccc2OCCF)CC1.Cl
InChIKey: YFHDJRXKUBGRGA-UHFFFAOYSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q01827
Assay: Inhibition of [3H]dopamine uptake at VMAT2 in rat striatal synaptic vesicles by scintillation spectrometry
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 385.52, ALogP 4.93, HBA 3, HBD 0, PSA 21.7, QED 0.58
Compound (SMILES): O=c1ccc2ccccc2[te]1
InChIKey: XKISACYHJSOTET-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated 15 mins prior to testing by CO2 hydration based stopped-flow assay
Measurement: Ki = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 257.75
Compound (SMILES): CC(C)Cc1ccc(C(C)C(=O)NCCCOc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: UBWFOFQYWMLOHJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 catalytic domain incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 418.56, ALogP 3.22, HBA 4, HBD 2, PSA 98.49, QED 0.58
Compound (SMILES): CCOC(=O)c1c(C)oc2cc(OCc3ccccc3)c(OCc3oc4cc(OCC5CCCCC5)c(OS(=O)(=O)[O-])cc4c3C(=O)OCC)cc12.[Na+]
InChIKey: RVIRXUKDYXNKEW-UHFFFAOYSA-M
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using spectrozyme TH as substrate pretreated for 10 mins followed by substrate addition measured in presence of 5 uM exosite 1 competitor hirudine peptide by spectrophotometric method
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 736.79, ALogP 8.14, HBA 12, HBD 1, PSA 170.17, QED 0.08
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-n3cnc4ccccc43)c12
InChIKey: XAHJWGOHTQLOMU-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 9.9 nM (pChEMBL 8)
Descriptors: MW 410.44, ALogP 4.73, HBA 7, HBD 1, PSA 94.65, QED 0.45
Compound (SMILES): CC(C)(CO)n1cc(C(=O)c2cncc(NC(=O)Cc3ccc(Cl)cn3)c2)c2cnc(N)nc21
InChIKey: BPIWZDNVMQQBQX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of dofetilide binding to human ERG
Measurement: Ki > 40300 nM (pChEMBL 4.394999980926514)
Descriptors: MW 479.93, ALogP 2.6, HBA 9, HBD 3, PSA 148.91, QED 0.34
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(C(=O)CN(C)C)C5)ncc3F)cc2n1C(C)C
InChIKey: SSVSKCKWUAPYHI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100x, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM x10000 was used as the final data for analysis.
Measurement: IC50 = 97.2 nM (pChEMBL 7.010000228881836)
Descriptors: MW 520.59, ALogP 4.25, HBA 8, HBD 1, PSA 92.07, QED 0.41
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)C(C)CC6)n3)nc2)CC1
InChIKey: YCANTYAOGZQCIG-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 504.59, ALogP 4.55, HBA 8, HBD 1, PSA 75, QED 0.41
Compound (SMILES): N#Cc1ccnc(N2C(=O)CC[C@H]2C(=O)N(c2cccc(F)c2)[C@@]2(C(=O)NC3CC(F)(F)C3)CCc3cc(Cl)ccc32)c1
InChIKey: BZJCZDVCLIWRFK-FKAPRUDGSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate pretreated for 60 mins followed by substrate addition measured after 60 mins by resazurin dye based fluorescence assay
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 608.02, ALogP 5.03, HBA 5, HBD 1, PSA 106.4, QED 0.42
Compound (SMILES): NCCCCNc1nc(Nc2ccc(CN3CCOCC3)cc2)c2ncn(C3CCCC3)c2n1
InChIKey: SBLIKFBWCULFJM-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of recombinant human 3C cleavage site/N-terminal GST-His6 fused PDGFR alpha C-terminal fragment (Q551 to L1089 residues) harboring V561D mutant expressed in baculovirus infected Sf9 insect cells using AGLT peptide as substrate in presence of [gamma-33P]-ATP
Measurement: IC50 = 188 nM (pChEMBL 6.730000019073486)
Descriptors: MW 464.62, ALogP 3.67, HBA 9, HBD 3, PSA 106.15, QED 0.39
Compound (SMILES): O=C(Cc1ccc(Cl)c(Cl)c1)N1CCOC2CNCC(N3CCCC3)C21
InChIKey: JMSHYBARLFGBPR-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]U-69,593 from kappa opioid receptor in guinea pig brain membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 398.33, ALogP 2.2, HBA 4, HBD 1, PSA 44.81, QED 0.85
Compound (SMILES): NS(=O)(=O)c1ccc(OCCNC(=O)Cc2ccccc2Nc2c(Cl)cccc2Cl)cc1
InChIKey: VNIROKIVWRXGRV-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 catalytic domain incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 144.4 nM (pChEMBL 6.840000152587891)
Descriptors: MW 494.4, ALogP 4.12, HBA 5, HBD 3, PSA 110.52, QED 0.39
Compound (SMILES): CC1(C)NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: QEQUHVRIJFFOKD-LMOJIFKQSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 875.99, ALogP -0.46, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): CCOC(=O)[C@@H]1CN(CCn2c(=O)[nH]c3ccccc3c2=O)CC[C@@H]1c1ccc(-c2ccccc2)cc1
InChIKey: FHKFHTMCQMFFEY-AOYPEHQESA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q05940
Assay: Inhibition of human VMAT2 expressed in HEK293 cell membranes assessed as reduction in [3H[-5HT uptake pre-incubated for 10 mins before [3H[-5HT addition and measured after 6 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 497.6, ALogP 4.03, HBA 6, HBD 1, PSA 84.4, QED 0.39
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-n3ccnc3)c12
InChIKey: RIDMLRBIZLZHIF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 335 nM (pChEMBL 6.46999979019165)
Descriptors: MW 360.38, ALogP 3.58, HBA 7, HBD 1, PSA 94.65, QED 0.53
Compound (SMILES): CC(C)[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2cscn2)c1)c1ccccc1
InChIKey: UTRPLZGACFVGID-FCHUYYIVSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Transrepression activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells assessed as inhibition of PMA-stimulated gene expression incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 470.55, ALogP 5.4, HBA 6, HBD 1, PSA 69.04, QED 0.37
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(-n2cc(-c3cncnc3)c3nc(N(C)C4CCN(CC)CC4)ccc32)c1F
InChIKey: AEJACXAFHXBVHF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant (unknown origin) by Z'-LYTE assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 569.68, ALogP 4.83, HBA 8, HBD 1, PSA 96.25, QED 0.31
Compound (SMILES): NCCCNC(=O)c1ccc(-c2cc(C(=O)O)cc(-n3cc(-c4ccc(C(F)(F)F)cc4)nn3)c2)s1
InChIKey: VYXSDIPOJBFWHQ-UHFFFAOYSA-N
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15391
Assay: Displacement of MRS4174 from human P2Y14R expressed in CHO cells preincubated for 30 mins followed by MRS4174 addition measured after 30 mins by flow cytometric method
Measurement: IC50 = 169 nM (pChEMBL 6.769999980926514)
Descriptors: MW 515.52, ALogP 4.46, HBA 7, HBD 3, PSA 123.13, QED 0.3
Compound (SMILES): COc1cccc(/C=C/C(=O)c2ccncc2)c1
InChIKey: SMEDYRIIZMHYEO-AATRIKPKSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of recombinant human CYP1A1 expressed in HEK293 cells using 7-ethoxyresorufin as substrate pretreated for 30 mins followed by substrate addition measured for 60 mins by fluorescence assay
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 239.27, ALogP 2.99, HBA 3, HBD 0, PSA 39.19, QED 0.61
Compound (SMILES): COC(=O)c1cc(-c2cn(C(C)C)c3ccccc23)n[nH]1
InChIKey: TUZFGQFWBUTVGZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 catalytic domain preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 283.33, ALogP 3.4, HBA 4, HBD 1, PSA 59.91, QED 0.75
Compound (SMILES): O=C(CCCCCCN(Cc1ccccc1)Cc1ccccc1)NO
InChIKey: DTZPKSVXYRJCGJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant HDAC8 (unknown origin) expressed in Escherichia coli using fluor de Lys(R) as substrate pretreated for 5 mins followed by substrate addition measured after 35 mins by fluorescence assay
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 340.47, ALogP 4.14, HBA 3, HBD 2, PSA 52.57, QED 0.37
Compound (SMILES): CN(Cc1ccccc1OCCCCC(C)(C)C(=O)O)C(=O)c1ccc(-c2ccco2)cc1
InChIKey: RDTZXAYSBVNVKN-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Activation of human PPARgamma LBD expressed in CHO-K1 cells by beta galactosidase enzyme fragment complement based fluorescence assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.55, ALogP 5.88, HBA 4, HBD 1, PSA 79.98, QED 0.37
Compound (SMILES): CC(C)[C@@H]1N=C(c2ccccc2F)c2cc(Cl)ccc2NC1=S
InChIKey: IIYOCBNZOLLZCM-INIZCTEOSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Positive allosteric modulation of M1 receptor Y179A/W400A mutant (unknown origin)
Measurement: EC50 = 178 nM (pChEMBL 6.75)
Descriptors: MW 346.86, ALogP 5.09, HBA 2, HBD 1, PSA 24.39, QED 0.77
Compound (SMILES): CC1(C)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: YSZTVMQFORZYJG-LUKCZKMGSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 839.96, ALogP -1.22, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): O=S(=O)(Nc1cc(-c2cnc3[nH]nc(-c4ccncc4)c3c2)cnc1Cl)c1ccccc1
InChIKey: JNQFWBSHMGXTQX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay
Measurement: IC50 = 4.37 nM (pChEMBL 8.359999656677246)
Descriptors: MW 462.92, ALogP 4.54, HBA 6, HBD 2, PSA 113.52, QED 0.37
Compound (SMILES): O=C(CSc1nc2c(c(=O)n1Cc1ccccc1)SCC2)Nc1nc2ccc(C(F)(F)F)cc2s1
InChIKey: AKDORUDVYNLYEP-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of human recombinant CK1epsilon using alpha-casein as substrate after 30 mins in presence of [gamma-32P]-ATP by Cherenkov counting method
Measurement: IC50 = 1410 nM (pChEMBL 5.849999904632568)
Descriptors: MW 534.61, ALogP 5.3, HBA 8, HBD 1, PSA 76.88, QED 0.27
Compound (SMILES): Cc1cc(OCCCN2CCN(c3ccccc3)CC2)ccc1Cl.Cl.Cl
InChIKey: RTHQQMXOILOELC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from recombinant human 5-HT6 receptor expressed in CHO cells cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 344.89, ALogP 4.24, HBA 3, HBD 0, PSA 15.71, QED 0.73
Compound (SMILES): O=C(Nc1c(-c2cccs2)nc2ccccn12)c1ccc(Cl)cc1
InChIKey: AZKMWHRDICVYEI-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6/beta-2/delta (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P18506
Assay: Modulation of rat eGFP-fused GABA-A receptor alpha6beta3delta expressed in HEK293 cells in presence of GABA by patch-clamp assay
Measurement: EC50 = 2290 nM (pChEMBL 5.639999866485596)
Descriptors: MW 353.83, ALogP 4.97, HBA 4, HBD 1, PSA 46.4, QED 0.56
Compound (SMILES): Fc1ccc(Cc2ccnc3c2CC[C@@H]2CNCCN32)cc1
InChIKey: PUZQIEAXLJCDIM-MRXNPFEDSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at recombinant 5-HT2A receptor (unknown origin) expressed in HEK293 cells assessed as increase in [3H]-inositol phosphate accumulation by scintillation counting method
Measurement: EC50 = 99.9 nM (pChEMBL 7)
Descriptors: MW 297.38, ALogP 2.54, HBA 3, HBD 1, PSA 28.16, QED 0.92
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Cc4ccc(CC(=O)NO)cc4)ccc3OCC)nc12
InChIKey: AFVWNFJXGSIJSF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human recombinant N-terminal GST-tagged HDAC6 expressed in baculovirus infected sf9 cells using fluorogenic HDAC substrate 3 after 30 mins by fluorescence assay
Measurement: IC50 = 162 nM (pChEMBL 6.789999961853027)
Descriptors: MW 475.55, ALogP 3.31, HBA 7, HBD 3, PSA 122.13, QED 0.25
Compound (SMILES): CN(C)C1CCN(c2ccc(Nc3cc4c(N5CCCC5)nc(Nc5ccccc5)nc4cn3)nc2)CC1
InChIKey: LGMJCNIZSXOQFC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR L858R/T790M/C797S mutant (unknown origin) using Poly (Glu, Tyr) as substrate after 40 mins by kinase-Glo luminescence assay
Measurement: IC50 = 62.2 nM (pChEMBL 7.210000038146973)
Descriptors: MW 509.66, ALogP 5.04, HBA 9, HBD 2, PSA 85.34, QED 0.36
Compound (SMILES): CCc1ccc(-c2cc(NCC3CCN(C)CC3)c3cc(OC)c(OCCCN4CCCC4)cc3n2)o1
InChIKey: PQJVPCANHLGIOZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of Tracer Red binding to human ERG in membranes after 2 hrs by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 506.69, ALogP 5.68, HBA 7, HBD 1, PSA 63, QED 0.34
Compound (SMILES): CN(C)C[C@H]1C2CCC(c3ccccc3)(C2)[C@H]1O
InChIKey: HGNFUCJMHJYHIN-ZTTSNEECSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Binding affinity to thrombin cleavable N-terminal 6His tagged and 13C-IVLM labeled human KDM4A tandem TUDOR domain (897 to 1011 residues) expressed in Escherichia coli BL21(DE3)-T1R assessed as apparent Kd for H3(1-10)K4me3 peptide at 0.5 mM by ITC method (Rvb = 5.2 +/- 0.3 uM)
Measurement: Kd = 15500 nM (pChEMBL 4.809999942779541)
Descriptors: MW 245.37, ALogP 2.28, HBA 2, HBD 1, PSA 23.47, QED 0.88
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O
InChIKey: VPDBSKOWEPRFMT-DZCXQCEKSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of PGPH activity of human 26S proteasome using Z-LLE-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 1366.62
Compound (SMILES): COC(=O)CNC(=O)NCc1ccc(C(=O)N2Cc3cnn(C)c3Nc3ccccc32)cc1C
InChIKey: XOYDUGXEXIVUAJ-UHFFFAOYSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Displacement of DY647 from SNAP-tagged OTR receptor (unknown origin) expressed in HEK293 cells by TR-FRET assay
Measurement: Ki = 385 nM (pChEMBL 6.420000076293945)
Descriptors: MW 462.51, ALogP 2.6, HBA 7, HBD 3, PSA 117.59, QED 0.5
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=[Se])Nc2ccc(F)cc2)cc1
InChIKey: WEUISFFZQUMPMK-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 catalytic domain preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 372.28
Compound (SMILES): CC(C)C[C@H]1CN(C2CCN(c3n[nH]c(N)n3)CC2)[C@@H](Cc2ccc(Cl)cc2)CN1C
InChIKey: RCGRIXXPKNDBJW-SFTDATJTSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Human CHIT1 Activity Assay: An enzymatic assay with recombinant human CHIT1 was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-methylumbelliferyl β-D-N,N′,N″-triacetylchitotriose was used as a substrate for the enzyme. Upon hydrolysis by CHIT1, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of CHIT1 recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Solution (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 446.04, ALogP 3.28, HBA 6, HBD 2, PSA 77.31, QED 0.71
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C
InChIKey: UZHRVXRQUPFWLS-RPXHOIECSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Displacement of N-Flu-DOT1L from MBP-tagged ENL (unknown origin) (489 to 559 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 7730 nM (pChEMBL 5.110000133514404)
Descriptors: MW 855.09, ALogP 0.87, HBA 9, HBD 6, PSA 226.66, QED 0.1
Compound (SMILES): CS(=O)(=O)N1CCN(Cc2cc3c(N4CCOCC4)nc(-c4cnc(N)nc4)c(Cl)n3n2)CC1
InChIKey: NOCRVEDBMWCMTR-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant full-length human N-terminal His6-tagged p110gamma expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate by HTRF assay
Measurement: Ki = 16.7 nM (pChEMBL 7.78000020980835)
Descriptors: MW 508.01, ALogP 0.34, HBA 11, HBD 1, PSA 135.08, QED 0.51
Compound (SMILES): CC(C)(O)[C@H](F)CNC(=O)C[C@@H]1CCc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1S(=O)(=O)c1ccc(F)cc1
InChIKey: FQWMGYJHFABALZ-FXAWDEMLSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at GAL4-tagged human LXRbeta assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 618.54, ALogP 4.26, HBA 5, HBD 3, PSA 106.94, QED 0.38
Compound (SMILES): O=S(=O)(Oc1ccccc1)C1CC2OC1C(c1ccc(/C=C/c3cc(O)cc(O)c3)cc1)=C2c1ccc(O)cc1
InChIKey: ZAZMBTKOZBHDGU-VOTSOKGWSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at human ERalpha expressed in HEK293T cells after 24 hrs by ERE-based dual luciferase reporter gene assay
Measurement: IC50 = 428 nM (pChEMBL 6.369999885559082)
Descriptors: MW 554.62, ALogP 5.83, HBA 7, HBD 3, PSA 113.29, QED 0.19
Compound (SMILES): CNc1ncc2c(-c3ccc(N4CCNCC4)nc3)nn(CC3CCCC3)c2n1
InChIKey: MMJWZGGVKOHMPQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of wild-type human partial length VEGFR2 (R787 to P1253 residues) expressed in mammalian expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 392.51, ALogP 2.53, HBA 8, HBD 2, PSA 83.79, QED 0.69
Compound (SMILES): c1ccc2c(NCCCCC[Se]CCCCCNc3c4c(nc5ccccc35)CCCC4)c3c(nc2c1)CCCC3
InChIKey: RFJOKGIIFYOSLX-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Non-competitive inhibition of electric eel AChE assessed as enzyme-substrate-inhibitor complex using p-nitrophenyl acetate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 613.75
Compound (SMILES): COc1cccc(Cn2c(SCC(=O)Nc3nc4ccc(C(F)(F)F)cc4s3)nc3c(c2=O)SCC3)c1OC
InChIKey: ASNBCMDJKIZLOU-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of human recombinant CK1epsilon using alpha-casein as substrate after 30 mins in presence of [gamma-32P]-ATP by Cherenkov counting method
Measurement: IC50 = 1230 nM (pChEMBL 5.909999847412109)
Descriptors: MW 594.66, ALogP 5.32, HBA 10, HBD 1, PSA 95.34, QED 0.22
Compound (SMILES): C=CC(=O)Nc1ccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3OC)ncc2Cl)cc1
InChIKey: JPEBHFDPUUEBJJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 6390 nM (pChEMBL 5.190000057220459)
Descriptors: MW 494.98, ALogP 4.55, HBA 8, HBD 2, PSA 91.85, QED 0.44
Compound (SMILES): NC(=O)c1cc2ccc(OC(F)(F)F)cc2n1-c1cc(CCC(=O)O)ccn1
InChIKey: KEQSTBYHFUWBLB-UHFFFAOYSA-N
Target: Group 10 secretory phospholipase A2 (SINGLE PROTEIN), Homo sapiens
UniProt: O15496
Assay: Inhibition of recombinant human sPLA2-10 using human HDL as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 393.32, ALogP 3.04, HBA 5, HBD 2, PSA 107.44, QED 0.67
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H](Cc2ccc(C#Cc3ccccc3)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1)C(=O)O
InChIKey: LWPABDJNWSXGPM-HZWOCANUSA-N
Target: Urotensin-2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKP6
Assay: Agonist activity at human UT receptor expressed in HEK293 cells co-expressing Gq-polycistronic BRET biosensor assessed as induction of Gq activation measured for 5 mins by luminescence detection based BRET assay
Measurement: EC50 = 27.54 nM (pChEMBL 7.559999942779541)
Descriptors: MW 1117.36
Compound (SMILES): CCC1Cc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCN(CC)CC6)cn5)ncc4F)cc3n2C1
InChIKey: UGRAFLUUHGUBAR-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 49700 nM (pChEMBL 4.300000190734863)
Descriptors: MW 518.62, ALogP 4.63, HBA 8, HBD 1, PSA 75, QED 0.38
Compound (SMILES): NC(=O)c1ccc(OCc2ccc(F)cc2)cc1
InChIKey: KYFVQTLQFWOEDC-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q53GL7
Assay: Inhibition of C-terminal His-tagged human ARTD10 (809 to 1017 residues) expressed in Escherichia coli Rosetta2 (DE3) using SRPK2 as substrate after 13 hrs in presence of NAD+
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 245.25, ALogP 2.5, HBA 2, HBD 1, PSA 52.32, QED 0.9
Compound (SMILES): CCCCNc1nc(N)nc2cccc(OCc3ccc(CO)cc3OC)c12
InChIKey: JKOASNLADJSLBV-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 382.46, ALogP 3.5, HBA 7, HBD 3, PSA 102.52, QED 0.49
Compound (SMILES): CN1CCN(C(=O)c2ccc(-c3ccc4ncc(-c5ccc(C#N)cc5)n4n3)cc2)CC1
InChIKey: PEHQJHHHTXOGJK-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: Inhibition of GST-tagged MNK1 (37 to 341 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) using JH3 peptide as substrate preincubated for 10 mins followed by substrate and ATP addition measured after 60 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 422.49, ALogP 3.32, HBA 6, HBD 0, PSA 77.53, QED 0.51
Compound (SMILES): COc1ccncc1NC(=O)c1ccnc(NC(=O)C2CC2)c1
InChIKey: NZMAVPMPPORZNT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK (unknown origin) by Ambit kinase assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 312.33, ALogP 2.09, HBA 5, HBD 2, PSA 93.21, QED 0.88
Compound (SMILES): CCOC(=O)[C@@H]1CN(CCn2c(=O)[nH]c3ccccc3c2=O)CC[C@@H]1c1cccc2c1OCCO2
InChIKey: NNVKSALIQZOGHN-YLJYHZDGSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q05940
Assay: Inhibition of human VMAT2 expressed in HEK293 cell membranes assessed as reduction in [3H[-5HT uptake pre-incubated for 10 mins before [3H[-5HT addition and measured after 6 mins
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 479.53, ALogP 2.13, HBA 8, HBD 1, PSA 102.86, QED 0.54
Compound (SMILES): Nc1nc2[nH]c(CCC#Cc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)nc3)cc2c(=O)[nH]1
InChIKey: VKYMIASYZYDIRX-HNNXBMFYSA-N
Target: Folate receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P14207
Assay: Binding affinity to human FR-beta receptor expressed in Chinese hamster D4 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs by Cell-Titer Blue assay
Measurement: IC50 = 18.8 nM (pChEMBL 7.730000019073486)
Descriptors: MW 452.43, ALogP 0.26, HBA 7, HBD 6, PSA 204.15, QED 0.26
Compound (SMILES): CC(C)[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2ccc(F)cc2)c1)c1ccccc1
InChIKey: BQFJIAVSQQVSTN-LOSJGSFVSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Transrepression activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells assessed as inhibition of PMA-stimulated gene expression incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: IC50 < 0.34 nM (pChEMBL 9.468999862670898)
Descriptors: MW 481.52, ALogP 6.08, HBA 4, HBD 1, PSA 56.15, QED 0.33