lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(-c2csc(Nc3ccc(O)c(C(=O)O)c3)n2)cc1C
InChIKey: JKAHVAHFZKSBFC-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PRMT5 (2 to end residues) /human N-terminal His-tagged MEP50 (2 to end residues) expressed in HEK293F cells using substrate pretreated for 15 mins followed by substrate and [3H]-SAM addition measured after 60 mins by scintillation proximity assay
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 356.4, ALogP 4.27, HBA 6, HBD 3, PSA 91.68, QED 0.59
Compound (SMILES): C=Cc1ccccc1C[C@@H](C(=O)NCC(N)=O)N(C)C(=O)[C@@H](C)NC(=O)[C@@H](N)Cc1c(C)cc(O)cc1C
InChIKey: QMSFTMNSMKWZSC-DKLXNKCPSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P32300
Assay: Agonist activity at delta-opioid receptor in mouse vasa deferens assessed as inhibition of electrically induced contractions
Measurement: IC50 = 0.689 nM (pChEMBL 9.15999984741211)
Descriptors: MW 523.63, ALogP 0.7, HBA 6, HBD 5, PSA 167.85, QED 0.27
Compound (SMILES): CC(=O)Nc1nc(C)c(-c2cc3c(c(S(N)(=O)=O)c2)C(=O)N([C@@H](C)C2CC2)C3)s1
InChIKey: NHFRWRZPNNFBRN-JTQLQIEISA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human 6His-tagged PI3K p110beta/p85alpha using DiC8-PIP2 as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 > 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 434.54, ALogP 2.48, HBA 6, HBD 2, PSA 122.46, QED 0.75
Compound (SMILES): Cc1cc(OCCN2CCOCC2)ccc1-c1cc2c(-c3ccc(C#N)c(C(C)C)c3)ccnc2[nH]1
InChIKey: QSTGCWGHXBTQEI-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of IKK1 (unknown origin)
Measurement: IC50 > 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 480.61, ALogP 5.91, HBA 5, HBD 1, PSA 74.17, QED 0.36
Compound (SMILES): CCCCCCCCCCCCCC(=S)NCCCC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1)C(=O)N[C@H](C(=O)NCC(=O)O)[C@@H](C)O
InChIKey: UEYXMOTVZNZSMM-NNKOJQEISA-N
Target: NAD-dependent protein deacylase sirtuin-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N6T7
Assay: Inhibition of human SIRT6 (1 to 294 residues) expressed in Escherichia coli Rosetta (DE3) using H3K9AcWW as substrate preincubated for 15 mins followed by substrate addition measured after 1 hr by HPLC analysis
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 756.07, ALogP 2.69, HBA 9, HBD 9, PSA 224.01, QED 0.04
Compound (SMILES): N=C(N)c1ccc(NC(=O)[C@H](NS(=O)(=O)c2ccc(F)cc2)C2CCCCC2)cc1
InChIKey: YNTJJZQMTAZQND-LJQANCHMSA-N
Target: Serine protease hepsin (SINGLE PROTEIN), Homo sapiens
UniProt: P05981
Assay: Inhibition of recombinant C-terminal His10-tagged human Hepsin (R45 to L17 residues) D161E/ R162K double mutant expressed in mouse NS0 cells using Boc-QRR-AMC as substrate after 15 mins by manual fluorescence assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 432.52, ALogP 2.98, HBA 4, HBD 4, PSA 125.14, QED 0.4
Compound (SMILES): NC(=O)c1ccc(Oc2cccc(C(=O)N3CCC(c4cccc(F)c4)CC3)c2)cc1
InChIKey: WZYQDWOOAZBCFD-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q53GL7
Assay: Inhibition of full length recombinant His6-tagged human PARP10 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 418.47, ALogP 4.74, HBA 3, HBD 1, PSA 72.63, QED 0.65
Compound (SMILES): COc1ccccc1-c1cc2c(-c3ccc(C(N)=O)c(C4CCCC4)c3)ccnc2[nH]1
InChIKey: HOQCCNALNBIQIM-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of IKK1 (unknown origin)
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 411.51, ALogP 5.66, HBA 3, HBD 2, PSA 81, QED 0.44
Compound (SMILES): NC(=O)c1c(O)cc(O)c2c1oc1c(=O)[nH]cnc12
InChIKey: PWJHRBPKGHHEDX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of recombinant human PIM1 using CREBtide as substrate after 60 mins by LANCE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 261.19, ALogP 0.18, HBA 6, HBD 4, PSA 142.44, QED 0.49
Compound (SMILES): COc1cccc(CNc2nc(N)c3nc(-c4ccccc4)sc3n2)c1
InChIKey: BCYGXPUZEWFUON-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B adenosine receptor assessed as inhibition of NECA-stimulated cAMP level after 30 mins by Alphascreen assay
Measurement: IC50 = 2387 nM (pChEMBL 5.619999885559082)
Descriptors: MW 363.45, ALogP 3.96, HBA 7, HBD 2, PSA 85.95, QED 0.56
Compound (SMILES): CC(=O)NS(=O)(=O)c1ccc(C2=NN(C(C)=O)C(c3ccc(Cl)cc3)O2)cc1
InChIKey: NJIRXSZMTROSSJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 assessed as reduction in CO2 hydration pretreated for 15 mins followed by CO2 addition measured for 10 to 100 sec by Line-Weaver Burk plot analysis
Measurement: Ki = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 421.86, ALogP 2.4, HBA 6, HBD 1, PSA 105.14, QED 0.82
Compound (SMILES): COc1ccc(-c2ccccc2)cc1Nc1nccc(-c2ccc(C(N)=O)cc2)n1
InChIKey: LQKXEYFFONHVCM-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: Inhibition of JNK1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 396.45, ALogP 4.66, HBA 5, HBD 2, PSA 90.13, QED 0.49
Compound (SMILES): COc1ccccc1CNc1nc(N)c2nc(C)sc2n1
InChIKey: QFOUQHHFGBJWPI-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B adenosine receptor assessed as inhibition of NECA-stimulated cAMP level after 30 mins by Alphascreen assay
Measurement: IC50 = 5538 nM (pChEMBL 5.260000228881836)
Descriptors: MW 301.38, ALogP 2.6, HBA 7, HBD 2, PSA 85.95, QED 0.77
Compound (SMILES): Cc1cc(-c2cnc3[nH]ccc3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: GUINRVXRHQCRST-LBPRGKRZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human 6His-tagged PI3K p110delta/p85alpha using DiC8-PIP2 as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 332.41, ALogP 3.69, HBA 3, HBD 1, PSA 61.88, QED 0.8
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1ccc(-c2sc(C(=O)N[C@H]3C[C@H](C(=O)O)C3)nc2CC2CCCCC2)c(C(F)(F)F)c1
InChIKey: TWYNUYIAZBTJDJ-QAQDUYKDSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4 positive T cells assessed as inhibition of IL17A production in human Th17 cells after 1 hr
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 601.71, ALogP 5.62, HBA 6, HBD 3, PSA 125.46, QED 0.36
Compound (SMILES): O=C(O[C@H]1CN2CCC1CC2)[C@@H]1COCC(c2ccccc2)(c2ccccc2)O1
InChIKey: FTFRVHRVNAJZCB-VXKWHMMOSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]NMS from recombinant human muscarinic M4 receptor expressed in CHOK1 cell membranes after 120 mins by scintillation counting method
Measurement: Ki = 1174.9 nM (pChEMBL 5.929999828338623)
Descriptors: MW 393.48, ALogP 2.98, HBA 5, HBD 0, PSA 48, QED 0.75
Compound (SMILES): CC(C)NS(=O)(=O)c1ccc(-c2sc(C(=O)N[C@H]3C[C@H](C(=O)O)C3)nc2CC2CCCCC2)c(C(F)F)c1Cl
InChIKey: WSERDBMTQCXVFU-WKILWMFISA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human whole blood assessed as reduction in IL17A production
Measurement: EC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 604.14, ALogP 5.8, HBA 6, HBD 3, PSA 125.46, QED 0.31
Compound (SMILES): N#Cc1ccc2[nH]cc(CCCCN3CCN(c4cccc5nc6c(c(N)c45)CCC6)CC3)c2c1
InChIKey: CCBFOQGVIFFPHI-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of SERT (unknown origin) expressed in HEK293 cells assessed as reduction in 5-HT uptake incubated for 30 mins
Measurement: IC50 = 22.1 nM (pChEMBL 7.659999847412109)
Descriptors: MW 464.62, ALogP 4.8, HBA 5, HBD 2, PSA 84.97, QED 0.4
Compound (SMILES): COc1ccc(C(OCCN2CCCC(C(=O)O)C2)(c2ccc(OC)cc2C)c2ccc(OC)cc2C)cc1
InChIKey: MYCVXSNMMSWHHG-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT3 expressed in HEK293 cells assessed as decrease in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition measured after 4 mins by liquid scintillation counting analysis
Measurement: IC50 = 28840.32 nM (pChEMBL 4.539999961853027)
Descriptors: MW 533.67, ALogP 5.43, HBA 6, HBD 1, PSA 77.46, QED 0.33
Compound (SMILES): Cc1c(OCCN2CCOCC2)cccc1-c1cc2c(-c3ccc(C(N)=O)cc3)ccnc2[nH]1
InChIKey: PSLDQEIGOZTJMS-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of IKK1 (unknown origin)
Measurement: IC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 456.55, ALogP 4.02, HBA 5, HBD 2, PSA 93.47, QED 0.44
Compound (SMILES): C[C@@H](C1CCCCC1)n1c(-c2cc3c(cc2Br)OCO3)nc2cc(C(=O)Nc3ccc(C#N)cc3)ccc21
InChIKey: FJAOGFGHTPYADT-SFHVURJKSA-N
Target: Proteinase-activated receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P55085
Assay: Antagonist activity at human PAR2
Measurement: IC50 < 2.5 nM (pChEMBL 8.60200023651123)
Descriptors: MW 571.48, ALogP 7.46, HBA 6, HBD 1, PSA 89.17, QED 0.27
Compound (SMILES): C[C@@]1(C(=O)O[C@@H]2CN3CCC2CC3)COCC(c2ccccc2)(c2ccccc2)O1
InChIKey: UUQSWYMJKUSTBX-VWNXMTODSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]NMS from recombinant human muscarinic M4 receptor expressed in CHOK1 cell membranes after 120 mins by scintillation counting method
Measurement: Ki = 2754.23 nM (pChEMBL 5.559999942779541)
Descriptors: MW 407.51, ALogP 3.37, HBA 5, HBD 0, PSA 48, QED 0.73
Compound (SMILES): O=C(Nc1cnc(-n2nccn2)c(Cl)c1)C1CCN(c2ncccc2Cl)CC1
InChIKey: MWGUQKCGKFUPHW-UHFFFAOYSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Inhibition of MALT1 in PMA-stimulated human Jurkat T cells assessed as reduction in IL2 level pretreated for 30 mins followed by PMA-stimulation measured after 5.5 hr by bioluminescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 418.29, ALogP 3.22, HBA 7, HBD 1, PSA 88.83, QED 0.7
Compound (SMILES): COc1cccc(CNc2nc(N)c3nc(C)sc3n2)c1
InChIKey: IFUSHKGAHYCHIQ-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B adenosine receptor assessed as inhibition of NECA-stimulated cAMP level after 30 mins by Alphascreen assay
Measurement: IC50 = 3516 nM (pChEMBL 5.449999809265137)
Descriptors: MW 301.38, ALogP 2.6, HBA 7, HBD 2, PSA 85.95, QED 0.77
Compound (SMILES): Cc1cc(-c2nccnc2N)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: VDRQLLHYWSMVRB-NSHDSACASA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human 6His-tagged PI3K p110delta/p85alpha using DiC8-PIP2 as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 308.38, ALogP 2.79, HBA 4, HBD 1, PSA 72.11, QED 0.95
Compound (SMILES): C[C@H](Nc1cc(F)cc(F)c1)c1cc(C(=O)NCCN(C)C)cc2ncc(N3CCOCC3)nc12
InChIKey: FVGWYTCJVNLXLY-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Binding affinity to wild-type human PIK3Cgamma (S144 to A1102 residues) expressed in mammalian expression system by KINOMEScan assay
Measurement: Kd = 4266 nM (pChEMBL 5.369999885559082)
Descriptors: MW 484.55, ALogP 3.21, HBA 7, HBD 2, PSA 82.62, QED 0.51
Compound (SMILES): C[C@@H](N[C@H]1CCN(c2ccc(CC(=O)O)cc2)C1)c1cccc2ccccc12.Cl.Cl
InChIKey: GGCDGPMTTKKELW-KJHBKDRRSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 374.48, ALogP 4.4, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CCSCc2ccc(cc2)SC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: NKSOIRAZKJHNSQ-SXXMFYQFSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Displacement of [3H]OT from human mammary gland oxytocin receptor expressed in HEK293 cell membrane after 1 hr by scintillation counting method
Measurement: Ki = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 1082.32
Compound (SMILES): O=C(Nc1nc2cccc(Cl)c2[nH]1)c1ccccc1
InChIKey: UYANATZTFXSNEV-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human A2B receptor expressed in cell membranes after 30 mins by beta-scintillation counting method
Measurement: Ki = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 271.71, ALogP 3.47, HBA 2, HBD 2, PSA 57.78, QED 0.75
Compound (SMILES): CC1(C)SSC(C)(C)[C@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N2CCN(CC2)C(=O)[C@H](Cc2ccccc2)NC(=O)CNC(=O)[C@H]1NC(=O)[C@@H](N)Cc1ccc(O)cc1
InChIKey: VVZPRTIRPLMIAE-RQBKSZSXSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at KOR (unknown origin) expressed in HEK cells assessed as reduction in cAMP accumulation by split luciferase assay
Measurement: EC50 = 269 nM (pChEMBL 6.570000171661377)
Descriptors: MW 1081.33
Compound (SMILES): Cc1nc2c(N)nc(Nc3ccccc3)nc2s1
InChIKey: JXMVGWKOLQYAPP-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B adenosine receptor assessed as inhibition of NECA-stimulated cAMP level after 30 mins by Alphascreen assay
Measurement: IC50 = 3725 nM (pChEMBL 5.429999828338623)
Descriptors: MW 257.32, ALogP 2.72, HBA 6, HBD 2, PSA 76.72, QED 0.74
Compound (SMILES): Nc1cccnc1N1CCC(C(=O)Nc2cnc(-n3nccn3)c(Cl)c2)CC1
InChIKey: XRLOYXFJBUUMBI-UHFFFAOYSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Inhibition of MALT1 in PMA-stimulated human Jurkat T cells assessed as reduction in IL2 level pretreated for 30 mins followed by PMA-stimulation measured after 5.5 hr by bioluminescence assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 398.86, ALogP 2.15, HBA 8, HBD 2, PSA 114.85, QED 0.69
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)Cc1ccccc1)C(=O)N[C@@H](Cc1ccc(N)cc1)CS(=O)(=O)F
InChIKey: NMPLEZOMBFJCJD-FWEHEUNISA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human 20S immunoproteasome beta-5 using Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 605.78, ALogP 2.23, HBA 7, HBD 5, PSA 173.48, QED 0.14
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1ccc(-c2sc(C(=O)N[C@H]3C[C@H](C(=O)O)C3)nc2CC2CCCCC2)c2ccccc12
InChIKey: KYIGOCCCBXRHNJ-MXVIHJGJSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human GAL4 DBD-fused RORgammat LBD (237 to 497 residues) expressed in HEK293T cells assessed as reduction in ROR mediated transcriptional activity after 24 hrs by dual glo luciferase reporter gene assay
Measurement: IC50 = 0.94 nM (pChEMBL 9.029999732971191)
Descriptors: MW 583.78, ALogP 5.76, HBA 6, HBD 3, PSA 125.46, QED 0.31
Compound (SMILES): Cc1c(CN2CCOCC2)cccc1-c1cc2c(-c3ccc(C(N)=O)cc3)ccnc2[nH]1
InChIKey: KASDTXOUSYBOPY-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of IKK1 (unknown origin)
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 426.52, ALogP 4.14, HBA 4, HBD 2, PSA 84.24, QED 0.5
Compound (SMILES): CC(=O)NS(=O)(=O)c1ccc(C2=NN(C(C)=O)C(c3ccc(Cl)cc3Cl)O2)cc1
InChIKey: KGHWWIIEPVNIMW-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 assessed as reduction in CO2 hydration pretreated for 15 mins followed by CO2 addition measured for 10 to 100 sec by Line-Weaver Burk plot analysis
Measurement: Ki = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 456.31, ALogP 3.06, HBA 6, HBD 1, PSA 105.14, QED 0.76
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(C(F)(F)F)cc1)C(=O)NCC(N)=O
InChIKey: CZDZZPIQDHMNJS-ZRBLBEILSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P32300
Assay: Agonist activity at delta-opioid receptor in mouse vasa deferens assessed as inhibition of electrically induced contractions
Measurement: IC50 = 1.78 nM (pChEMBL 8.75)
Descriptors: MW 636.68, ALogP -0.03, HBA 7, HBD 9, PSA 238.54, QED 0.07
Compound (SMILES): CC1(C)c2cccc(C(=O)NO)c2CN1c1nc2ncccc2o1
InChIKey: PLKUOGQAYYNHLT-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: In Vitro Histone Deacetylase Assay II: The measurement of HD AC 11 deacetylase activity was performed using an electrophoretic mobility shift assay by Nanosyn (Santa Clara, Calif.). Full length human recombinant HD AC 11 protein was expressed in baculoviral system and purified by affinity chromatography. The enzymatic reactions were assembled in 384 well plates in a total volume of 25 μL in a reaction buffer composing: 100 mM HEPES, pH 7.5, 25 mM KCl, 0.1% bovine serum albumin, 0.01% Triton X-100, 1% DMSO (from compounds), 2 μM of the fluorescently labeled peptide substrate and enzyme. The enzyme was added at a final concentration of 10 nM. The peptide substrate FAM-RHKK(tri-fluor-Ac)NH2 was used. The compounds were tested at 12 concentrations spaced by 3× dilution intervals. Negative control samples (0%-inhibition in the absence of inhibitor) and positive control samples (100%-inhibition) were assembled in replicates of four in each assay plate. The reactions were incubated at 25° C. and quenched by the addition of 45 μL of termination buffer (100 mM HEPES, pH 7.5, 0.01% Triton X-100, 0.05% SDS).The terminated assay plates were analyzed on LabChip® 3000 microfluidic electrophoresis instrument (Perkin Elmer/Caliper Life Sciences). The fluorescence intensity of the electrophoretically separated de-acetylated product and substrate peptide was measured. Activity in each sample was determined as the product to sum ratio (PSR): P/(S+P), where P is the peak height of the product peptide and S is the peak height of the substrate peptide. Percent inhibition (Pinh) is determined using the following equation:P inh=(PSR0%−PSRinh)/(PSR0%−PSR100%)*100,where PSRinh, is the product sum ratio in the presence of inhibitor, PSR0% is the average product sum ration in the absence of inhibitor and PSR100% is the average product sum ratio in 100%-inhibition control samples. The IC50 values of inhibitors were determined by fitting the percent inhibition curves with 4 parameter dose-response model using XLfit 4 software.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 324.34, ALogP 2.6, HBA 6, HBD 2, PSA 91.49, QED 0.56
Compound (SMILES): NC(=O)c1ccc(Oc2cccc(C(=O)N3CCN(c4ccc(F)cc4)CC3)c2)cc1
InChIKey: MFXVNPUAZXWGLT-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of full length recombinant His6-tagged human PARP1 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 419.46, ALogP 3.68, HBA 4, HBD 1, PSA 75.87, QED 0.68
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1ccc(-c2sc(C(=O)N3CCC(C)(C(=O)O)C3)nc2CC2CCCCC2)c2ccccc12
InChIKey: LQIMYRLGJBRBMG-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4 positive T cells assessed as inhibition of IL17A production in human Th17 cells after 1 hr
Measurement: EC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 597.8, ALogP 6.1, HBA 6, HBD 2, PSA 116.67, QED 0.34
Compound (SMILES): CN1CCN(c2cc(-c3ccncc3)c(-c3ccc4ccccc4c3)nn2)CC1
InChIKey: CIIVUDIZZJLXCN-UHFFFAOYSA-N
Target: Casein kinase I isoform delta (SINGLE PROTEIN), Homo sapiens
UniProt: P48730
Assay: Inhibition of human CK1delta
Measurement: IC50 = 2610 nM (pChEMBL 5.579999923706055)
Descriptors: MW 381.48, ALogP 4.11, HBA 5, HBD 0, PSA 45.15, QED 0.53
Compound (SMILES): COC(=O)c1ccc2[nH]cc(CCCCN3CCN(c4cccc5nc6c(c(N)c45)CCCC6)CC3)c2c1
InChIKey: UDFDEEOQQQUXBN-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of SERT (unknown origin) expressed in HEK293 cells assessed as reduction in 5-HT uptake incubated for 30 mins
Measurement: IC50 = 314.1 nM (pChEMBL 6.5)
Descriptors: MW 511.67, ALogP 5.11, HBA 6, HBD 2, PSA 87.48, QED 0.26
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NC3CCS(=O)(=O)CC3)nc2CC2CC2)c2ccccc12)C(F)(F)F
InChIKey: FMKRUXVKAZQWTL-HNNXBMFYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human whole blood assessed as reduction in IL17A production
Measurement: EC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 615.72, ALogP 4.45, HBA 7, HBD 2, PSA 122.3, QED 0.39
Compound (SMILES): COc1ccccc1Nc1nccc(-c2ccc(C(N)=O)cc2)n1
InChIKey: DLBMFLKYVCPNBQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: Inhibition of JNK1 (unknown origin)
Measurement: IC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 320.35, ALogP 2.99, HBA 5, HBD 2, PSA 90.13, QED 0.75
Compound (SMILES): CN(C)C(=O)c1cc(C2CCCN2c2cc(F)cc(F)c2)c2nc(N3CCOCC3)cnc2c1
InChIKey: PNYSVXYTVOTZHS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Binding affinity to wild-type human PIK3Cgamma (S144 to A1102 residues) expressed in mammalian expression system by KINOMEScan assay
Measurement: Kd = 1318 nM (pChEMBL 5.880000114440918)
Descriptors: MW 467.52, ALogP 3.79, HBA 6, HBD 0, PSA 61.8, QED 0.58
Compound (SMILES): O=C(NO)c1cccc2c1CCN(c1nc3ccccc3[nH]1)CC2
InChIKey: ZLVLSTLRFFQNOK-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: In Vitro Histone Deacetylase Assay II: The measurement of HD AC 11 deacetylase activity was performed using an electrophoretic mobility shift assay by Nanosyn (Santa Clara, Calif.). Full length human recombinant HD AC 11 protein was expressed in baculoviral system and purified by affinity chromatography. The enzymatic reactions were assembled in 384 well plates in a total volume of 25 μL in a reaction buffer composing: 100 mM HEPES, pH 7.5, 25 mM KCl, 0.1% bovine serum albumin, 0.01% Triton X-100, 1% DMSO (from compounds), 2 μM of the fluorescently labeled peptide substrate and enzyme. The enzyme was added at a final concentration of 10 nM. The peptide substrate FAM-RHKK(tri-fluor-Ac)NH2 was used. The compounds were tested at 12 concentrations spaced by 3× dilution intervals. Negative control samples (0%-inhibition in the absence of inhibitor) and positive control samples (100%-inhibition) were assembled in replicates of four in each assay plate. The reactions were incubated at 25° C. and quenched by the addition of 45 μL of termination buffer (100 mM HEPES, pH 7.5, 0.01% Triton X-100, 0.05% SDS).The terminated assay plates were analyzed on LabChip® 3000 microfluidic electrophoresis instrument (Perkin Elmer/Caliper Life Sciences). The fluorescence intensity of the electrophoretically separated de-acetylated product and substrate peptide was measured. Activity in each sample was determined as the product to sum ratio (PSR): P/(S+P), where P is the peak height of the product peptide and S is the peak height of the substrate peptide. Percent inhibition (Pinh) is determined using the following equation:P inh=(PSR0%−PSRinh)/(PSR0%−PSR100%)*100,where PSRinh, is the product sum ratio in the presence of inhibitor, PSR0% is the average product sum ration in the absence of inhibitor and PSR100% is the average product sum ratio in 100%-inhibition control samples. The IC50 values of inhibitors were determined by fitting the percent inhibition curves with 4 parameter dose-response model using XLfit 4 software.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 322.37, ALogP 2.29, HBA 4, HBD 3, PSA 81.25, QED 0.5
Compound (SMILES): CC(=O)NS(=O)(=O)c1ccc(C2=NN(C(C)=O)C(c3ccc(C(F)(F)F)cc3)O2)cc1
InChIKey: HXTBGAXRNAXQBD-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 assessed as reduction in CO2 hydration pretreated for 15 mins followed by CO2 addition measured for 10 to 100 sec by Line-Weaver Burk plot analysis
Measurement: Ki = 53.8 nM (pChEMBL 7.269999980926514)
Descriptors: MW 455.41, ALogP 2.77, HBA 6, HBD 1, PSA 105.14, QED 0.76
Compound (SMILES): CC1(C)c2cccc(C(=O)NO)c2CN1c1ccc(C(F)(F)F)cn1
InChIKey: LKTXDGRWJDTGPL-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of NanoLuc-tagged HDAC11 (unknown origin) by BRET assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 351.33, ALogP 3.47, HBA 4, HBD 2, PSA 65.46, QED 0.64
Compound (SMILES): CN1CCN(c2ccc(Nc3cc4c(N[C@@H]5CCCN(C)C5)nc(Nc5ccccc5)nc4cn3)nc2)CC1
InChIKey: BLEXFAVHCWOELK-JOCHJYFZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S triple mutant (unknown origin) using Poly(Glu,Tyr) as substrate after 40 mins by Kinase-Glo luminescence assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 524.68, ALogP 4.16, HBA 10, HBD 3, PSA 97.37, QED 0.33
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CCSCc2cccc(c2)CSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: FNUGQFWBEQQYTP-HKITYUSYSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Displacement of [3H]OT from human mammary gland oxytocin receptor expressed in HEK293 cell membrane after 1 hr by scintillation counting method
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 1096.34
Compound (SMILES): O=C(N[C@@H](Cn1ccnc1)c1ccc(Cl)cc1Cl)c1ccc(-c2nnc(-c3ccc(F)c(F)c3)o2)cc1
InChIKey: AZQFCMJDNRLROF-QHCPKHFHSA-N
Target: Putative lanosterol 14-alpha-demethylase (SINGLE PROTEIN), Leishmania infantum
UniProt: A2TEF2
Assay: Binding affinity to Leishmania infantum CYP51 expressed in Escherichia coli
Measurement: Kd = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 540.36, ALogP 6.36, HBA 6, HBD 1, PSA 85.84, QED 0.26
Compound (SMILES): CC(C)(O)CNC(=O)c1nc(CC2CCCCC2)c(-c2ccc(S(=O)(=O)NC(C)(C)C)c3ccccc23)s1
InChIKey: YBTHMLBUJBBJME-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 557.78, ALogP 5.66, HBA 6, HBD 3, PSA 108.39, QED 0.33
Compound (SMILES): C=CC(=O)N[C@@H]1CCCN(c2nc(Nc3ccccc3)nc3cnc(Nc4ccc(N5CCN(C)CC5)cn4)cc23)C1
InChIKey: WEFQZVAPJGXAMW-HSZRJFAPSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S triple mutant (unknown origin) using Poly(Glu,Tyr) as substrate after 40 mins by Kinase-Glo luminescence assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 564.7, ALogP 3.93, HBA 10, HBD 3, PSA 114.44, QED 0.27
Compound (SMILES): COc1ccccc1Nc1ncc(F)c(-c2ccc(C(=O)O)c(C(C)C)c2)n1
InChIKey: CNCIHPWJSBLKSU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: Inhibition of JNK1 (unknown origin)
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 381.41, ALogP 4.86, HBA 5, HBD 2, PSA 84.34, QED 0.63
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)CS(=O)(=O)F
InChIKey: RHJVXRZDRSZJEL-FWEHEUNISA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human 20S immunoproteasome beta-5 using Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 699.89, ALogP 2.44, HBA 8, HBD 7, PSA 221.67, QED 0.04
Compound (SMILES): C[C@H](Nc1cccc(F)c1)c1cc(C(=O)NCCO)cc2ncc(N3CCOCC3)nc12
InChIKey: ZTTPIMYWVRADFY-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Binding affinity to wild-type human PIK3Cgamma (S144 to A1102 residues) expressed in mammalian expression system by KINOMEScan assay
Measurement: Kd = 2851 nM (pChEMBL 5.539999961853027)
Descriptors: MW 439.49, ALogP 2.5, HBA 7, HBD 3, PSA 99.61, QED 0.52
Compound (SMILES): O=C(NO)c1cccc2c1CN(c1nc3ccccc3[nH]1)C2
InChIKey: WPCDPURYAICIPJ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: In Vitro Histone Deacetylase Assay II: The measurement of HD AC 11 deacetylase activity was performed using an electrophoretic mobility shift assay by Nanosyn (Santa Clara, Calif.). Full length human recombinant HD AC 11 protein was expressed in baculoviral system and purified by affinity chromatography. The enzymatic reactions were assembled in 384 well plates in a total volume of 25 μL in a reaction buffer composing: 100 mM HEPES, pH 7.5, 25 mM KCl, 0.1% bovine serum albumin, 0.01% Triton X-100, 1% DMSO (from compounds), 2 μM of the fluorescently labeled peptide substrate and enzyme. The enzyme was added at a final concentration of 10 nM. The peptide substrate FAM-RHKK(tri-fluor-Ac)NH2 was used. The compounds were tested at 12 concentrations spaced by 3× dilution intervals. Negative control samples (0%-inhibition in the absence of inhibitor) and positive control samples (100%-inhibition) were assembled in replicates of four in each assay plate. The reactions were incubated at 25° C. and quenched by the addition of 45 μL of termination buffer (100 mM HEPES, pH 7.5, 0.01% Triton X-100, 0.05% SDS).The terminated assay plates were analyzed on LabChip® 3000 microfluidic electrophoresis instrument (Perkin Elmer/Caliper Life Sciences). The fluorescence intensity of the electrophoretically separated de-acetylated product and substrate peptide was measured. Activity in each sample was determined as the product to sum ratio (PSR): P/(S+P), where P is the peak height of the product peptide and S is the peak height of the substrate peptide. Percent inhibition (Pinh) is determined using the following equation:P inh=(PSR0%−PSRinh)/(PSR0%−PSR100%)*100,where PSRinh, is the product sum ratio in the presence of inhibitor, PSR0% is the average product sum ration in the absence of inhibitor and PSR100% is the average product sum ratio in 100%-inhibition control samples. The IC50 values of inhibitors were determined by fitting the percent inhibition curves with 4 parameter dose-response model using XLfit 4 software.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 294.31, ALogP 2.2, HBA 4, HBD 3, PSA 81.25, QED 0.5
Compound (SMILES): COc1ccccc1CNc1nc(N)c2nc(-c3ccccc3)sc2n1
InChIKey: REDHRMQBZHBARB-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Antagonist activity at human A1 adenosine receptor expressed in CHO cells assessed as inhibition of CCPA-induced reduction of forskolin-stimulated cAMP level after 30 mins by Alphascreen assay
Measurement: IC50 = 13.4 nM (pChEMBL 7.869999885559082)
Descriptors: MW 363.45, ALogP 3.96, HBA 7, HBD 2, PSA 85.95, QED 0.56
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)n(C(C)C)c(=O)c3cnc(Nc4ccc(N5CCN(C)CC5)cc4OC)nc32)c1
InChIKey: RLWORZOMJGXPLR-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 570.65, ALogP 3.15, HBA 11, HBD 2, PSA 126.62, QED 0.31
Compound (SMILES): O=C(O)c1ccc(-c2ccnc(Nc3cccc(-c4ccccc4)c3)n2)cc1
InChIKey: UHSGKZKFUUFRPH-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 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 367.41, ALogP 5.25, HBA 4, HBD 2, PSA 75.11, QED 0.5
Compound (SMILES): Cc1ccc(CN2CCOCC2)cc1-c1cc2c(-c3ccc(C(N)=O)cc3)ccnc2[nH]1
InChIKey: REBMHIWSAFBPLI-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of INSR (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 426.52, ALogP 4.14, HBA 4, HBD 2, PSA 84.24, QED 0.5
Compound (SMILES): CCCc1cc(F)ccc1[C@H](O)c1ncc[nH]1
InChIKey: IDFPQEHZYBXIFO-LBPRGKRZSA-N
Target: Proteinase-activated receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P55085
Assay: Trypin Activated FLPR Assay: Calcium mobilization was measured using 1321N1 cells stably expressing human PAR2. Cells were seeded in 384-well plates at 4,000 cells per well in 20 μl DMEM with Glutamax supplemented with 10% FBS and incubated for 18-24 h at 37° C., 5% CO2 and 95% humidity. Cells were loaded with 20 μl Fluo-8 NW calcium dye (Cat: 36316, AAT Bioquest) and kept at 37° C. for 30 min prior to addition of 10 μl compound prepared in 20 mM HEPES pH 7.4, HBSS, 2.5% DMSO, 0.1% BSA and 6 μM Vorapaxar (to block Trypsin induced activity of PAR1). The addition was done using a FLIPRTETRA (384-well head, Molecular Devices) and the response was read simultaneously to detect any agonist activity. The cells were incubated for 30 min at room temperature with the compounds and were then evaluated for antagonist activity by addition of 10 μl 234 nM Trypsin prepared in 20 mM HEPES pH 7.4, HBSS and 0.1% BSA and simultaneous detection of calcium mobilization using the FLIPRTETRA.
Measurement: IC50 = 3920 nM (pChEMBL 5.409999847412109)
Descriptors: MW 234.27, ALogP 2.58, HBA 2, HBD 2, PSA 48.91, QED 0.85
Compound (SMILES): C[C@]1(C(=O)O[C@H]2CN3CCC2CC3)COCC(c2ccccc2)(c2ccccc2)O1
InChIKey: UUQSWYMJKUSTBX-LADGPHEKSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from recombinant human muscarinic M5 receptor expressed in CHOK1 cell membranes after 120 mins by scintillation counting method
Measurement: Ki = 363.08 nM (pChEMBL 6.440000057220459)
Descriptors: MW 407.51, ALogP 3.37, HBA 5, HBD 0, PSA 48, QED 0.73
Compound (SMILES): CC(=O)Nc1nc(C)c(-c2cc3c(c(NS(C)(=O)=O)c2)C(=O)N([C@@H](C)C2CC2)C3)s1
InChIKey: RMZMULPZUXWJGE-NSHDSACASA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human 6His-tagged PI3K p110delta/p85alpha using DiC8-PIP2 as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 448.57, ALogP 3.2, HBA 6, HBD 2, PSA 108.47, QED 0.71
Compound (SMILES): CNCCNC(=O)c1cc(C(C)Nc2cccc(F)c2)c2nc(N3CCOCC3)cnc2c1
InChIKey: MUSGURQXGKSPBK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to wild-type human MTOR (L1382 to W2549 residues) expressed in mammalian expression system by KINOMEScan assay
Measurement: Kd = 23442 nM (pChEMBL 4.630000114440918)
Descriptors: MW 452.53, ALogP 2.73, HBA 7, HBD 3, PSA 91.41, QED 0.45
Compound (SMILES): C[C@@]1(C(=O)O[C@H]2CN3CCC2CC3)COCC(c2ccccc2)(c2ccccc2)O1
InChIKey: UUQSWYMJKUSTBX-UPVQGACJSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from recombinant human muscarinic M5 receptor expressed in CHOK1 cell membranes after 120 mins by scintillation counting method
Measurement: Ki = 467.74 nM (pChEMBL 6.329999923706055)
Descriptors: MW 407.51, ALogP 3.37, HBA 5, HBD 0, PSA 48, QED 0.73
Compound (SMILES): Cc1cncc(-c2ccc(C(=O)N(c3ncccc3Cl)[C@@H]3CCCNC3)cc2)n1
InChIKey: ZRWWXYPLGSDQJG-GOSISDBHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 407.9, ALogP 3.9, HBA 5, HBD 1, PSA 71.01, QED 0.71
Compound (SMILES): COc1ccc(C(/C=C/CN2CCCC(C(=O)O)C2)(c2ccc(OC)cc2)c2ccc(OC)cc2)cc1
InChIKey: RNLUGOUUDNQOGZ-PTXOJBNSSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cells assessed as decrease in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition measured after 4 mins by liquid scintillation counting analysis
Measurement: IC50 = 2137.96 nM (pChEMBL 5.670000076293945)
Descriptors: MW 501.62, ALogP 5.4, HBA 5, HBD 1, PSA 68.23, QED 0.3
Compound (SMILES): c1cc(C2CCC3(CC2)OOC2(OO3)C3CC4CC(C3)CC2C4)ccc1CN1CCOCC1
InChIKey: FVBMLPSUVONWLN-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes assessed as midazolam 1'-hydroxylation after 4 to 40 mins in presence of NADPH by LCMS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 455.6, ALogP 4.94, HBA 6, HBD 0, PSA 49.39, QED 0.6
Compound (SMILES): Cc1c(F)cccc1NCc1cc(C(=O)NCCN(C)C)cc2ncc(N3CCOCC3)nc12
InChIKey: RENMFICGXZWWQK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to wild-type human MTOR (L1382 to W2549 residues) expressed in mammalian expression system by KINOMEScan assay
Measurement: Kd = 17783 nM (pChEMBL 4.75)
Descriptors: MW 466.56, ALogP 2.82, HBA 7, HBD 2, PSA 82.62, QED 0.53
Compound (SMILES): N#CCCc1ccc(-c2nc3cnc4[nH]ccc4c3n2C2CCCCC2)o1
InChIKey: PLKGAHIHTTYWEV-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of human TYK2 using KKSRGDYMTMQIG as substrate in presence of 10 uM [gamma33P]ATP by radiometric method
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 359.43, ALogP 5.13, HBA 5, HBD 1, PSA 83.43, QED 0.55
Compound (SMILES): COc1ccc(C(=O)C2=C(O)C(=O)N(c3ccc(-c4ccon4)cc3)C2C2CCCCC2)cc1
InChIKey: VVVNQMHFXWAMBD-UHFFFAOYSA-N
Target: P2X purinoceptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51575
Assay: Antagonist activity at P2X1 receptor (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 458.51, ALogP 5.34, HBA 6, HBD 1, PSA 92.87, QED 0.5
Compound (SMILES): COc1ccccc1Nc1nccc(-c2ccc(C(N)=O)c(C(C)C)c2)n1
InChIKey: BWXJXZTVSHIZDT-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 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 362.43, ALogP 4.12, HBA 5, HBD 2, PSA 90.13, QED 0.69
Compound (SMILES): COc1ccc2c(NC(C)Cc3cc(C)[nH]n3)ncnc2c1OC
InChIKey: JTROLECZHRVLFM-UHFFFAOYSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q14123
Assay: Inhibition of recombinant C-terminal FLAG tagged human PDE1C expressed in HEK293 cells using 3',5'-[3H]cGMP as substrate
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 327.39, ALogP 2.72, HBA 6, HBD 2, PSA 84.95, QED 0.72
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1ccc(-c2sc(C(=O)NC34CC(C(=O)O)(C3)C4)nc2CC2CCCCC2)c2ccccc12
InChIKey: IXZNFUVIMHGHCV-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human whole blood assessed as reduction in IL17A production
Measurement: EC50 = 404 nM (pChEMBL 6.389999866485596)
Descriptors: MW 595.79, ALogP 5.9, HBA 6, HBD 3, PSA 125.46, QED 0.3
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CCSCc2ccccc2CSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: QFLOUMLKTQRCOG-HKITYUSYSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Agonist activity at human mammary gland oxytocin receptor expressed in CHO cells assessed as increase in intracellular calcium flux measured for 5 mins by Fluo-4-AM dye based FLIPR assay
Measurement: EC50 = 294 nM (pChEMBL 6.53000020980835)
Descriptors: MW 1096.34
Compound (SMILES): COc1ccccc1Nc1ncc(F)c(-c2ccc(C(N)=O)c(C(C)C)c2)n1
InChIKey: GNUXXWKKCHYOLW-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 380.42, ALogP 4.26, HBA 5, HBD 2, PSA 90.13, QED 0.67
Compound (SMILES): C[C@@H](Nc1cccc(F)c1)c1cc(C(=O)NCCO)cc2ncc(N3CCOCC3)nc12
InChIKey: ZTTPIMYWVRADFY-OAHLLOKOSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to wild-type human MTOR (L1382 to W2549 residues) expressed in mammalian expression system by KINOMEScan assay
Measurement: Kd = 17128 nM (pChEMBL 4.769999980926514)
Descriptors: MW 439.49, ALogP 2.5, HBA 7, HBD 3, PSA 99.61, QED 0.52
Compound (SMILES): CC(=O)Nc1nc(C)c(-c2cc(Cl)c3c(c2)CN([C@H](C)C2CC2)C3=O)s1
InChIKey: SDQPODDUDFEPDG-SNVBAGLBSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHG7
Assay: Inhibition of PI3Kgamma in mouse RAW264 cells assessed as reduction in Akt phosphorylation at Ser473 residue preincubated for 15 mins followed by C5a stimulation measured after 3 mins by TR-FRET assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 389.91, ALogP 4.48, HBA 4, HBD 1, PSA 62.3, QED 0.84
Compound (SMILES): Clc1ccc(SSc2nccs2)cc1
InChIKey: VWPWGCSEEUQWCP-UHFFFAOYSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of human liver FBPase C179S mutant expressed in Escherichia coli BL21 (DE3) using FBP as substrate incubated for 5 mins by malachite green dye based assay
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 259.81, ALogP 4.6, HBA 4, HBD 0, PSA 12.89, QED 0.75
Compound (SMILES): NC(=O)c1c(O)cc(O)c2c1oc1c(N)ncnc12
InChIKey: YROMDBCZHPOCDZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Inhibition of human haspin using full-length histone H3 as substrate after 10 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.21, ALogP 0.47, HBA 7, HBD 4, PSA 148.49, QED 0.5
Compound (SMILES): C[C@H](NC(=O)c1cc(-c2sc(C(=O)N[C@H]3C[C@H](C(=O)O)C3)nc2CC2CCCCC2)cc(C(C)(C)C)c1)C(F)(F)F
InChIKey: GZCDNIGGYFEPLV-BUKVSMQUSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4 positive T cells assessed as inhibition of IL17A production in human Th17 cells after 1 hr
Measurement: EC50 = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 593.71, ALogP 6.5, HBA 5, HBD 3, PSA 108.39, QED 0.32
Compound (SMILES): CC(C)OC(=O)[C@H](Cn1ccnc1)NC(=O)c1cc(-c2ccccc2F)on1
InChIKey: NPLGDPLOUGTYDQ-INIZCTEOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated for 10 mins followed by NADPH addition measured after 10 mins by LC/MS/MS analysis
Measurement: IC50 = 5810 nM (pChEMBL 5.239999771118164)
Descriptors: MW 386.38, ALogP 2.43, HBA 7, HBD 1, PSA 99.25, QED 0.63
Compound (SMILES): CS(=O)(=O)Nc1cccc(-c2cc3c(-c4ccc(C(N)=O)cc4)ccnc3[nH]2)c1
InChIKey: SOIQVEVFDNZKNF-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of INSR (unknown origin)
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 406.47, ALogP 3.37, HBA 4, HBD 3, PSA 117.94, QED 0.47
Compound (SMILES): CCn1ncc2c1CC[C@@H](Nc1nc3c(-c4ccc(F)cc4C)cccn3n1)C2
InChIKey: OHXQPMCUJTWQJA-QGZVFWFLSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 390.47, ALogP 4.03, HBA 6, HBD 1, PSA 60.04, QED 0.57
Compound (SMILES): C[C@H](NC(=O)c1cc(-c2sc(C(=O)N[C@H]3C[C@H](C(=O)O)C3)nc2CC2CCCCC2)cc(C2(C)CC2)c1)C(F)(F)F
InChIKey: PSFPATVFAWGHAJ-BUKVSMQUSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4 positive T cells assessed as inhibition of IL17A production in human Th17 cells after 1 hr
Measurement: EC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 591.7, ALogP 6.26, HBA 5, HBD 3, PSA 108.39, QED 0.32
Compound (SMILES): CNC(=O)c1ccccc1Oc1nc(Nc2cc(OC)c(OC)c(OC)c2)ncc1Br
InChIKey: NEXGBSJERNQRSV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: ULK1 inhibition assay: Gamma-32P assays to measure ULK1 kinase activity were performed as previously described. Briefly, Flag ULK1 was transfected into HEK293T cells and 20 hours later treated as indicated. The immmunoprecipitate was washed in IP buffer 3 times, and washed in kinase buffer (25 mM MOPS, pH 7.5, 1 mM EGTA, 0.1 mM Na3VO4, 15 mM MgCl2,). Hot and cold ATP were added at a 100 μM final concentration. As substrates, GST or the recombinant protein GST-Atg101 purified from E. coli were used at 1 μg for each reaction. Reactions were boiled, run out on SDS page gel. The gel was dried, and imaged using PhosphoImager software. For cold assays to asses ULK1, Flag ULK1 which was transiently overexpressed and immunoprecipited from HEK293T cells. Reactions were then run out on SDS page gel, transferred to PVDF membrane and blotted for total levelsFluorescence MicroscopyVps34flox/flox MEFs were reconstituted with Flag-VPS34 and either p40FX or GFP-DFCP1. 48 hours post infection with adenovirus expressing Cre recombinase (MOI of 100), cells were plated on glass coverslips at a density of 3×105 cells per well in 6-well tissue culture plates. 18 h later, cells were fixed in 4% PFA in PBS for 10 minutes and permeabilized in 0.2% Triton in PBS for 10 minutes. The following primary antibodies were used: mouse anti-Myc epitope and LC3B XP antibody (2276 and 3868 respectively, Cell Signaling Technologies). Secondary antibodies were anti-rabbit Alexa488 and anti-mouse Alexa594 (Molecular Probes, 1:1000. Cells were then fixed and counter stained with DAPI. Coverslips were mounted in FluoromountG (SouthernBiothech). Images were acquired on a Zeiss Axioplan2 epifluorescence microscope coupled to the Openlab software. Confocal images of mitotracker were taken on Zeiss LSM 710 laser scanning confocal microscope. 10 random fields per condition were acquired using the 100× objective and representative images shown. Glass coverslips were mounted directly on plate with FluoromountG and images taken on Zeiss Axioplan2 epifluorescence microscope.
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 489.33, ALogP 4.16, HBA 8, HBD 2, PSA 103.83, QED 0.49