lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H](CCCNCCCn1ccnc1)[C@H]1CC[C@@]2(C)[C@@H]3CC=C4[C@@H](CC[C@H](O)C4(C)C)[C@]3(C)[C@H](O)C[C@]12C
InChIKey: LENXTOOUMVYVFH-GVOOPAHWSA-N
Target: AMPK alpha2/beta1/gamma1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P54646
Assay: Allosteric activation of AMPK alpha2/beta1/gamma1 in human HepG2 cells by scintillation proximity assay
Measurement: EC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 525.82, ALogP 6.22, HBA 5, HBD 3, PSA 70.31, QED 0.26
Compound (SMILES): Cn1nccc1[C@H]1CCC[C@@H]1Oc1ccc(S(=O)(=O)Nc2ccncn2)c(F)c1F
InChIKey: WMJRYBDMGFCCAB-OCCSQVGLSA-N
Target: Sodium channel protein type 1 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P35498
Assay: Inhibition of human NaV1.1/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 435.46, ALogP 3, HBA 7, HBD 1, PSA 99, QED 0.64
Compound (SMILES): Cc1noc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(F)c(F)c2F)n1
InChIKey: QGDYFWSKNIXGOV-TXWAPCLOSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 473.5, ALogP 4.03, HBA 8, HBD 1, PSA 84.9, QED 0.57
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccccc4-c4ccccc4)cccn23)cn1.Cl
InChIKey: SNJBKRNVFBEXET-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 462.55, ALogP 5.7, HBA 5, HBD 1, PSA 68.52, QED 0.34
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccccc4)cccn23)cn1.Cl
InChIKey: ZEBCPOCLNPTTPZ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 386.46, ALogP 4.03, HBA 5, HBD 1, PSA 68.52, QED 0.54
Compound (SMILES): Fc1ccc(C2CCCn3nc(N[C@@H]4[C@@H]5CC[C@H]4CN(c4ccnc(C(F)(F)F)c4)C5)nc32)c(F)c1F
InChIKey: KXIPKBDNWGDNKQ-XYQMTRTISA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 522.5, ALogP 5.36, HBA 6, HBD 1, PSA 58.87, QED 0.37
Compound (SMILES): Cc1noc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)F)ccc(C(F)(F)F)n3n2)n1
InChIKey: CXJQWJBRXYDTFP-GNXNZQSNSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 491.4, ALogP 3.71, HBA 9, HBD 1, PSA 93.61, QED 0.54
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(C(F)(F)F)cc2)ncn1
InChIKey: HAOUFCWTXNTIAB-ZGSMLMOQSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 497.57, ALogP 5.04, HBA 7, HBD 1, PSA 71.76, QED 0.54
Compound (SMILES): Cc1nsc(N2CC3CCC(C2)C3Nc2nc3c(-c4ccc(F)c(F)c4F)cccn3n2)n1
InChIKey: IAINSZMFDDIZGX-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 471.51, ALogP 4.3, HBA 8, HBD 1, PSA 71.24, QED 0.45
Compound (SMILES): Cn1nccc1[C@H]1CCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)c(F)c1
InChIKey: PDNOJYMMZNQRJD-KDOFPFPSSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human NaV1.5/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 449.48, ALogP 3.39, HBA 7, HBD 1, PSA 99, QED 0.62
Compound (SMILES): Cn1nccc1[C@H]1CCC[C@@H]1Oc1ccc(S(=O)(=O)Nc2ccncn2)c(F)c1F
InChIKey: WMJRYBDMGFCCAB-OCCSQVGLSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human NaV1.5/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 = 84000 nM (pChEMBL 4.079999923706055)
Descriptors: MW 435.46, ALogP 3, HBA 7, HBD 1, PSA 99, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc([S+]([O-])Cc4ncc(C(C)(C)C)o4)s3)C2)cc1
InChIKey: CCGRMLGTKGCLKM-DEQHTHAUSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of recombinant human full-length His-tagged CDK7/Cyclin H/MNAT1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr by Alexa Fluor 647 ADP Tracer-based Adapta assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 541.7, ALogP 4.58, HBA 8, HBD 2, PSA 123.42, QED 0.32
Compound (SMILES): Cn1nccc1[C@H]1CCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)c(F)c1
InChIKey: PDNOJYMMZNQRJD-KDOFPFPSSA-N
Target: Sodium channel protein type 9 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human NaV1.7/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 449.48, ALogP 3.39, HBA 7, HBD 1, PSA 99, QED 0.62
Compound (SMILES): Cn1nccc1[C@H]1CCC[C@@H]1Oc1ccc(S(=O)(=O)Nc2ccncn2)c(F)c1F
InChIKey: WMJRYBDMGFCCAB-OCCSQVGLSA-N
Target: Sodium channel protein type 9 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human NaV1.7/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 = 495 nM (pChEMBL 6.300000190734863)
Descriptors: MW 435.46, ALogP 3, HBA 7, HBD 1, PSA 99, QED 0.64
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)cc1
InChIKey: RUBYHLPRZRMTJO-FLVSMNSFSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of recombinant full length human CDK7/C-terminal His-tagged Cyclin H/N-terminal GST-tagged MAT1 expressed in baculovirus in Sf21 insect cells using peptide substrate incubated for 30 mins in presence of [32P]gamma-ATP by scintillation counter method
Measurement: IC50 = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 558.09, ALogP 5.05, HBA 6, HBD 3, PSA 106.25, QED 0.26
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3nnc(SCc4ncc(C(C)(C)C)o4)s3)C2)cc1
InChIKey: ZGTBRXCHDKWPQT-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of recombinant human full-length His-tagged CDK7/Cyclin H/MNAT1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr by Alexa Fluor 647 ADP Tracer-based Adapta assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 526.69, ALogP 4.96, HBA 9, HBD 2, PSA 113.25, QED 0.31
Compound (SMILES): Cn1nccc1[C@H]1CCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)c(F)c1
InChIKey: PDNOJYMMZNQRJD-KDOFPFPSSA-N
Target: Sodium channel protein type 9 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q62205
Assay: Inhibition of mouse NaV1.7/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 449.48, ALogP 3.39, HBA 7, HBD 1, PSA 99, QED 0.62
Compound (SMILES): Cn1nccc1[C@H]1CCC[C@@H]1Oc1ccc(S(=O)(=O)Nc2ccncn2)c(F)c1F
InChIKey: WMJRYBDMGFCCAB-OCCSQVGLSA-N
Target: Sodium channel protein type 9 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q62205
Assay: Inhibition of mouse NaV1.7/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 435.46, ALogP 3, HBA 7, HBD 1, PSA 99, QED 0.64
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NO[C@H](c2cc(F)c(F)c(F)c2)[C@@H]3CO)ccc1-n1cnc(C)c1
InChIKey: OLTJQPQTIFFPOR-MBRPJUNBSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulation of gamma secretase in HEK293 cells transfected with human APP with Swedish and London familial AD mutation assessed as reduction in Abeta42 levels incubated for 5 hrs by sandwich immuno-assay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 498.51, ALogP 4.53, HBA 7, HBD 1, PSA 72.11, QED 0.52
Compound (SMILES): Cc1nnc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OC(C)C(F)(F)F)cccn3n2)o1
InChIKey: PYPNIGUSVUTKEM-IBHQRGPUSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 437.43, ALogP 3.08, HBA 9, HBD 1, PSA 93.61, QED 0.65
Compound (SMILES): Cc1noc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(F)c(F)c2F)n1
InChIKey: QGDYFWSKNIXGOV-TXWAPCLOSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 473.5, ALogP 4.03, HBA 8, HBD 1, PSA 84.9, QED 0.57
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccccc4-c4ccccc4)cccn23)cn1.Cl
InChIKey: SNJBKRNVFBEXET-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 462.55, ALogP 5.7, HBA 5, HBD 1, PSA 68.52, QED 0.34
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccccc4)cccn23)cn1.Cl
InChIKey: ZEBCPOCLNPTTPZ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 386.46, ALogP 4.03, HBA 5, HBD 1, PSA 68.52, QED 0.54
Compound (SMILES): Fc1ccc(C2CCCn3nc(N[C@@H]4[C@@H]5CC[C@H]4CN(c4ccnc(C(F)(F)F)c4)C5)nc32)c(F)c1F
InChIKey: KXIPKBDNWGDNKQ-XYQMTRTISA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 522.5, ALogP 5.36, HBA 6, HBD 1, PSA 58.87, QED 0.37
Compound (SMILES): Cc1noc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)F)ccc(C(F)(F)F)n3n2)n1
InChIKey: CXJQWJBRXYDTFP-GNXNZQSNSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 491.4, ALogP 3.71, HBA 9, HBD 1, PSA 93.61, QED 0.54
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(C(F)(F)F)cc2)ncn1
InChIKey: HAOUFCWTXNTIAB-ZGSMLMOQSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 497.57, ALogP 5.04, HBA 7, HBD 1, PSA 71.76, QED 0.54
Compound (SMILES): Cc1nsc(N2CC3CCC(C2)C3Nc2nc3c(-c4ccc(F)c(F)c4F)cccn3n2)n1
InChIKey: IAINSZMFDDIZGX-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 471.51, ALogP 4.3, HBA 8, HBD 1, PSA 71.24, QED 0.45
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NO[C@H](c2cc(F)c(F)c(F)c2)[C@@H]3CO)ccc1-n1cnc(C)c1
InChIKey: OLTJQPQTIFFPOR-MBRPJUNBSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma secretase in HEK293 cells transfected with human APP with Swedish and London familial AD mutation assessed as reduction in Abeta42 levels incubated for 5 hrs by sandwich immuno-assay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 498.51, ALogP 4.53, HBA 7, HBD 1, PSA 72.11, QED 0.52
Compound (SMILES): Cc1nnc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OC(C)C(F)(F)F)cccn3n2)o1
InChIKey: PYPNIGUSVUTKEM-IBHQRGPUSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 437.43, ALogP 3.08, HBA 9, HBD 1, PSA 93.61, QED 0.65
Compound (SMILES): Cc1noc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(F)c(F)c2F)n1
InChIKey: QGDYFWSKNIXGOV-TXWAPCLOSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 473.5, ALogP 4.03, HBA 8, HBD 1, PSA 84.9, QED 0.57
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccccc4-c4ccccc4)cccn23)cn1.Cl
InChIKey: SNJBKRNVFBEXET-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 462.55, ALogP 5.7, HBA 5, HBD 1, PSA 68.52, QED 0.34
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccccc4)cccn23)cn1.Cl
InChIKey: ZEBCPOCLNPTTPZ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 386.46, ALogP 4.03, HBA 5, HBD 1, PSA 68.52, QED 0.54
Compound (SMILES): Fc1ccc(C2CCCn3nc(N[C@@H]4[C@@H]5CC[C@H]4CN(c4ccnc(C(F)(F)F)c4)C5)nc32)c(F)c1F
InChIKey: KXIPKBDNWGDNKQ-XYQMTRTISA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 522.5, ALogP 5.36, HBA 6, HBD 1, PSA 58.87, QED 0.37
Compound (SMILES): Cc1noc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)F)ccc(C(F)(F)F)n3n2)n1
InChIKey: CXJQWJBRXYDTFP-GNXNZQSNSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 491.4, ALogP 3.71, HBA 9, HBD 1, PSA 93.61, QED 0.54
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(C(F)(F)F)cc2)ncn1
InChIKey: HAOUFCWTXNTIAB-ZGSMLMOQSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 497.57, ALogP 5.04, HBA 7, HBD 1, PSA 71.76, QED 0.54
Compound (SMILES): Cc1nsc(N2CC3CCC(C2)C3Nc2nc3c(-c4ccc(F)c(F)c4F)cccn3n2)n1
InChIKey: IAINSZMFDDIZGX-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 471.51, ALogP 4.3, HBA 8, HBD 1, PSA 71.24, QED 0.45
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NO[C@H](c2cc(F)c(F)c(F)c2)[C@@H]3CO)ccc1-n1cnc(C)c1
InChIKey: OLTJQPQTIFFPOR-MBRPJUNBSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma secretase in HEK293 cells transfected with human APP with Swedish and London familial AD mutation assessed as reduction in Abeta42 levels incubated for 5 hrs by sandwich immuno-assay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 498.51, ALogP 4.53, HBA 7, HBD 1, PSA 72.11, QED 0.52
Compound (SMILES): Cc1nnc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OC(C)C(F)(F)F)cccn3n2)o1
InChIKey: PYPNIGUSVUTKEM-IBHQRGPUSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 437.43, ALogP 3.08, HBA 9, HBD 1, PSA 93.61, QED 0.65
Compound (SMILES): Cc1noc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(F)c(F)c2F)n1
InChIKey: QGDYFWSKNIXGOV-TXWAPCLOSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 473.5, ALogP 4.03, HBA 8, HBD 1, PSA 84.9, QED 0.57
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccccc4-c4ccccc4)cccn23)cn1.Cl
InChIKey: SNJBKRNVFBEXET-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 462.55, ALogP 5.7, HBA 5, HBD 1, PSA 68.52, QED 0.34
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccccc4)cccn23)cn1.Cl
InChIKey: ZEBCPOCLNPTTPZ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 386.46, ALogP 4.03, HBA 5, HBD 1, PSA 68.52, QED 0.54
Compound (SMILES): Fc1ccc(C2CCCn3nc(N[C@@H]4[C@@H]5CC[C@H]4CN(c4ccnc(C(F)(F)F)c4)C5)nc32)c(F)c1F
InChIKey: KXIPKBDNWGDNKQ-XYQMTRTISA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 522.5, ALogP 5.36, HBA 6, HBD 1, PSA 58.87, QED 0.37
Compound (SMILES): Cc1noc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)F)ccc(C(F)(F)F)n3n2)n1
InChIKey: CXJQWJBRXYDTFP-GNXNZQSNSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 491.4, ALogP 3.71, HBA 9, HBD 1, PSA 93.61, QED 0.54
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(C(F)(F)F)cc2)ncn1
InChIKey: HAOUFCWTXNTIAB-ZGSMLMOQSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 497.57, ALogP 5.04, HBA 7, HBD 1, PSA 71.76, QED 0.54
Compound (SMILES): Cc1nsc(N2CC3CCC(C2)C3Nc2nc3c(-c4ccc(F)c(F)c4F)cccn3n2)n1
InChIKey: IAINSZMFDDIZGX-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 471.51, ALogP 4.3, HBA 8, HBD 1, PSA 71.24, QED 0.45
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCc3cccc4ccccc34)cn2)c1
InChIKey: HJHPUQDFLVHFFZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 343.39, ALogP 4.04, HBA 4, HBD 1, PSA 68.01, QED 0.59
Compound (SMILES): CC(Nc1nc(Nc2ccnc(C3(C#N)CC3)c2)nc(-c2cccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: HJCRKYCQHOQKKS-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 494.4, ALogP 5.01, HBA 8, HBD 2, PSA 112.3, QED 0.46
Compound (SMILES): FC1(F)CC(Nc2nc(Nc3ccnc(C(F)(F)F)c3)nc(-c3nc(C(F)(F)F)cs3)n2)C1
InChIKey: FIHMFIIGBKKTHS-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 497.38, ALogP 5.38, HBA 8, HBD 2, PSA 88.51, QED 0.46
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CC4(C3)CC(F)(F)C4)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: RHCDZLRZYCRNDX-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 490.43, ALogP 5.54, HBA 6, HBD 2, PSA 75.62, QED 0.54
Compound (SMILES): O=C(O)c1ccnc(-n2nc(C3CC3)cc2O)c1
InChIKey: WEZPYYZPYXGXHK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in Escherichia coli using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 245.24, ALogP 1.55, HBA 5, HBD 2, PSA 88.24, QED 0.86
Compound (SMILES): NC(=[Se])c1ccc(S(N)(=O)=O)cc1
InChIKey: CZIIHSLWIYNAMW-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of recombinant human carbonic anhydrase 5b incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 552.7 nM (pChEMBL 6.260000228881836)
Descriptors: MW 263.18
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(N)n2)n1)C1CC1
InChIKey: PRARPIBZHWEZPY-GHMZBOCLSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: In Vitro Assays for IDH2m R140Q Inhibitors: Compounds are assayed for IDH2 R140Q inhibitory activity through a cofactor depletion assay. Compounds are preincubated with enzyme, then the reaction is started by the addition of NADPH and α-KG, and allowed to proceed for 60 minutes under conditions previously demonstrated to be linear with respect for time for consumption of both cofactor and substrate. The reaction is terminated by the addition of a second enzyme, diaphorase, and a corresponding substrate, resazurin. Diaphorase reduces resazurin to the highly fluorescent resorufin with the concomitant oxidation of NADPH to NADP, both halting the IDH2 reaction by depleting the available cofactor pool and facilitating quantitation of the amount of cofactor remaining after a specific time period through quantitative production of an easily detected fluorophore.Specifically, into each of 12 wells of a 384-well plate, 1 μl of 100× compound dilution series is placed, followed by the addition of 40 μl of buffer (50 mM potassium phosphate (K2HPO4), pH 7.5; 150 mM NaCl; 10 mM MgCl2, 10% glycerol, 0.05% bovine serum albumin, 2 mM beta-mercaptoethanol) containing 0.25 μg/ml IDH2 R140Q protein. The test compound is then incubated for one hour at room temperature with the enzyme; before starting the IDH2 reaction with the addition of 10 μl of substrate mix containing 4 μM NADPH and 1.6 mM α-KG in the buffer described above. After a further 16 hours of incubation at room temperature, the reaction is halted and the remaining NADPH measured through conversion of resazurin to resorufin by the addition of 25 μl Stop Mix (36 μg/ml diaphorase enzyme and 60 μM resazurin; in buffer). After one minute of incubation the plate is read on a plate reader at Ex544/Em590.For determination of the inhibitory potency of compounds against IDH2 R140Q in an assay format similar to the above, a similar procedure is performed, except that the final testing concentration is 0.25 μg/ml IDH2 R140Q protein, 4 μM NADPH and 1.6 mM α-KG.For determination of the inhibitory potency of compounds against IDH2 R140Q in a high throughput screening format, a similar procedure is performed, except that 0.25 μg/ml IDH2 R140Q protein is utilized in the preincubation step, and the reaction is started with the addition of 4 μM NADPH and 8 μM α-KG.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 339.45, ALogP 2.94, HBA 7, HBD 3, PSA 101.64, QED 0.71
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NC3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)c1
InChIKey: NTKHRYLRDAXKRH-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 479.39, ALogP 5.31, HBA 7, HBD 2, PSA 99.41, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(/N=c2\scc(-c3ccc(Cl)cc3)n2-c2ccccc2)cc1
InChIKey: YXKRBFIZRCEMLB-FLFQWRMESA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 expressed in baculovirus infected sf21 cells assessed as reduction in formation of oxidized TMPD using arachidonic acid as substrate preincubated for 3 to 5 mins followed by arachidonic acid addition measured for 25 secs by spectrophotometric assay
Measurement: IC50 = 16210 nM (pChEMBL 4.789999961853027)
Descriptors: MW 441.97, ALogP 4.74, HBA 5, HBD 1, PSA 77.45, QED 0.5
Compound (SMILES): FC(F)c1cncc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)n1
InChIKey: NNVCNVORYXXOAM-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 475.44, ALogP 5.25, HBA 7, HBD 2, PSA 88.51, QED 0.55
Compound (SMILES): COc1ccc(N(CCCCN2CCC(O)(c3ccc(Cl)c(C(F)(F)F)c3)CC2)c2ccc(OC)cc2)cc1
InChIKey: DYLSSJRMONSQGQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]Mesulergine from human 5-HT2C receptor expressed in HEK293FlpIN cells by radioligand binding assay
Measurement: Ki = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 563.06, ALogP 7.28, HBA 5, HBD 1, PSA 45.17, QED 0.26
Compound (SMILES): Fc1cc(F)c(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1F
InChIKey: MRBFFDHADFWESD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 uM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 uM sodium L-ascorbate, 5 uM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen Streptavidin-coated Donor beads, and AlphaScreen Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 ug/ml beads.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 438.33, ALogP 4.41, HBA 5, HBD 1, PSA 72.28, QED 0.37
Compound (SMILES): C[C@@H](Nc1nc(NC(C(F)(F)F)C(F)(F)F)nc(-c2cccc(Cl)n2)n1)C(F)(F)F
InChIKey: VTJODCQTJUKOPV-RXMQYKEDSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 468.71, ALogP 4.85, HBA 6, HBD 2, PSA 75.62, QED 0.48
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCN3CCc4cc(F)ccc43)cn2)c1
InChIKey: VBYNYZPZKXJUEM-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 352.37, ALogP 2.85, HBA 5, HBD 1, PSA 71.25, QED 0.76
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H](Cc1ccc(Cl)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(C)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(N)=O
InChIKey: LAGYTFPAISIXPZ-ZXYZSCNASA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Agonist activity at human MC1R expressed in HEK293 cells after 3 mins by cAMP assay
Measurement: EC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 677.21, ALogP 2.21, HBA 6, HBD 7, PSA 203.96, QED 0.09
Compound (SMILES): COc1ccc2ccc3c(c2c1)C(CNC(C)=O)CC3
InChIKey: VABVTFAPCKMYHN-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Agonist activity at human MT2 receptor expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 269.34, ALogP 3.01, HBA 2, HBD 1, PSA 38.33, QED 0.93
Compound (SMILES): CCCCCCCCCCCCC/C(=N\O)c1cc(-c2ccc(O)c(F)c2)ccc1O
InChIKey: HDOKJCNJHOXSDX-ZZIIXHQDSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of FAAH in human U937 cells using [ethanolamine-1-3H]AEA as substrate pretreated for 30 mins followed by substrate addition and measured after 15 mins by liquid scintillation counting method
Measurement: IC50 = 8700 nM (pChEMBL 5.059999942779541)
Descriptors: MW 429.58, ALogP 7.78, HBA 4, HBD 3, PSA 73.05, QED 0.12
Compound (SMILES): Nc1ccccc1NC(=O)CCCCCCC(=O)Nc1ccc(-c2cn(Cc3ccccc3)nn2)cc1
InChIKey: IYKIQDXPWYJSPM-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using (FAM)-labeled acetylated peptide as substrate measured after 17 hrs by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 496.62, ALogP 5.49, HBA 6, HBD 3, PSA 114.93, QED 0.18
Compound (SMILES): FC1(F)CC(Nc2nc(NC3CC(F)(F)C3)nc(-c3nccc(C(F)(F)F)n3)n2)C1
InChIKey: FPHDGFLOXFTVGJ-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 437.32, ALogP 3.77, HBA 7, HBD 2, PSA 88.51, QED 0.69
Compound (SMILES): Cc1nn(C(=O)[C@H](C)c2ccc(CC(C)C)cc2)c(C)c1Cl
InChIKey: RFAYOJJBVSPOFY-GFCCVEGCSA-N
Target: Ectonucleoside triphosphate diphosphohydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97687
Assay: Inhibition of rat NTPDase1 expressed in CHO cells using ATP as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by malachite green reagent-based assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 318.85, ALogP 4.8, HBA 3, HBD 0, PSA 34.89, QED 0.81
Compound (SMILES): NC(=O)c1cnc2c(N[C@H]3C[C@H]3F)cc(Nc3cccc(-c4ccc(C(F)(F)F)cc4F)c3)nn12
InChIKey: UMHAGOZMLWBAGB-SJORKVTESA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in human whole blood assessed as decrease in IFNalpha-induced IP10 production
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 488.42, ALogP 4.92, HBA 6, HBD 3, PSA 97.34, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ncc(C[Te]c3ccccc3)[se]2)cc1
InChIKey: XIBJCSLHJGQWSV-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of recombinant human carbonic anhydrase 5b incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 504.93
Compound (SMILES): CCC(Nc1nc(NC(CC)C(F)(F)F)nc(-c2cccc(Cl)n2)n1)C(F)(F)F
InChIKey: SDUBFPITPDQUSW-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 442.8, ALogP 5.09, HBA 6, HBD 2, PSA 75.62, QED 0.46
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NC3CCC(F)(F)C3)nc(-n3ccc(C(F)(F)F)n3)n2)c1
InChIKey: GOMGSGWMVHCJSA-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 468.37, ALogP 4.43, HBA 8, HBD 2, PSA 104.34, QED 0.53
Compound (SMILES): CC(C#N)Nc1nc(Nc2ccnc(C(C)(F)F)c2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: DOYNKYWVGHFSIP-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 450.38, ALogP 4.53, HBA 8, HBD 2, PSA 112.3, QED 0.53
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1CN(S(=O)(=O)c2cccc(C#N)c2)CC12CC2
InChIKey: DHEBFJJCQBLOPI-KRWDZBQOSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Inhibition Test: Kinases used were human-derived JAK1, JAK2, JAK3, and TYK2 (Millipore, Germany). Each of these kinases was diluted with a suitable buffer solution as described below, and then mixed with reagents. Kinase-activity inhibitory effects of some of the compounds of Examples 1 to 73 (for example, Examples 5, 55, and 66) for JAK1, JAK2, JAK3, and TYK2 were measured at various concentrations by the above-described method, and IC50 values were determined. The IC50 values of the test compounds were calculated from % inhibition values of the compounds, by the Cheng-Prusoff method (Biochem. Pharmacol. (1973) 22, 3099-3108).
Measurement: IC50 = 58.6 nM (pChEMBL 7.230000019073486)
Descriptors: MW 408.49, ALogP 2.12, HBA 6, HBD 1, PSA 105.98, QED 0.71
Compound (SMILES): NC(=O)c1cnc2c(NC3CC3)cc(Nc3ccccc3)nn12
InChIKey: QZGWYLPGPJWINC-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in IL23-stimulated human Kit225 T cells by luciferase reporter assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 308.35, ALogP 2.15, HBA 6, HBD 3, PSA 97.34, QED 0.67
Compound (SMILES): Cc1nn(-c2cc(C(=O)O)ccn2)c(O)c1-c1ccccc1
InChIKey: VMLMHVMQZCMCBR-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 295.3, ALogP 2.65, HBA 5, HBD 2, PSA 88.24, QED 0.78
Compound (SMILES): Cc1cc(C)c(Nc2ccnc(Nc3ccc(Cl)cc3)n2)c(C)c1
InChIKey: UKMJJMHWYKEQMZ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of recombinant HIV1 reverse transcriptase Y188L mutant
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 338.84, ALogP 5.54, HBA 4, HBD 2, PSA 49.84, QED 0.66
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-n2ccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: ZFCNVKABVPLJJM-NXEZZACHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 381.41, ALogP 3.5, HBA 7, HBD 2, PSA 80.55, QED 0.76
Compound (SMILES): CC(F)(F)c1cccc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)n1
InChIKey: YRSZQQILDIHZRT-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 432.37, ALogP 4.46, HBA 6, HBD 2, PSA 75.62, QED 0.66
Compound (SMILES): O=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1n[nH]nc1O
InChIKey: CTPZCVRODHKARO-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Inhibition of IKK-beta in human Jurkat cells assessed as reduction in TNFalpha-stimulated IkBalpha degradation preincubated for 60 mins followed by TNFalpha stimulation for 20 mins by immunoblot analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 340.18, ALogP 2.8, HBA 4, HBD 3, PSA 90.9, QED 0.73
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ncc(-c3ccccc3)[se]2)cc1
InChIKey: FMNYHPPTHRSLST-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of recombinant human carbonic anhydrase 5b incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 703.1 nM (pChEMBL 6.150000095367432)
Descriptors: MW 363.3
Compound (SMILES): Fc1cccc(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)c1
InChIKey: BBWOOOREENNAAQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 6B (SINGLE PROTEIN), Homo sapiens
UniProt: O15054
Assay: JMJD3 Assay: The ability of test compounds to inhibit the activity of JMJD3 was determined in 384-well plate format under the following reaction conditions: 1 nM JMJD3, 250 nM H3K27me3-biotin labeled peptide (Anaspec cat #64367), 1 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K27me1 antibody, 5 μg/ml ALPHASCREEN® Streptavidin-coated Donor beads, and 5 μl g/ml ALPHASCREEN® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 10 mM EDTA, 2 mg/ml BSA.The assay reaction was initiated by the following: 3 μl of the mixture of 750 nM H3K27me3-biotin labeled peptide and 3 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 3 nM JMJD3 to initiate the reaction. The reaction mixture is incubated at rt for 20 min, and terminated by the addition of 3 μl of appropriate dilution of anti-H3K27me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 10 mM EDTA, 2 mg/ml BSA. Plates will then incubated at rt for 1 hr, followed by addition of 3 μl of 25 μg/ml ALPHASCREEN® Streptavidin-coated Donor beads and ALPHASCREEN® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 10 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hr incubation at rt. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 402.36, ALogP 4.13, HBA 5, HBD 1, PSA 72.28, QED 0.51
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NCC3CC3)nc(-c3cccc(C(F)(F)F)n3)n2)c1
InChIKey: MVIKPHSCGJFANI-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 429.38, ALogP 4.53, HBA 7, HBD 2, PSA 99.41, QED 0.56
Compound (SMILES): NC(=O)c1ccc(OCc2cccc(Br)c2)cc1
InChIKey: WNYIDDKTEYNPSM-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q53GL7
Assay: Inhibition of PARP10 (809 to 1017 residues) (unknown origin) expressed in Escherichia coli using NAD+ as substrate incubated for 13 hrs by fluorescence based assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 306.16, ALogP 3.13, HBA 2, HBD 1, PSA 52.32, QED 0.94
Compound (SMILES): CC1(NC#N)CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: PTCVBQDKOCSZKC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 = 97 nM (pChEMBL 7.010000228881836)
Descriptors: MW 289.34, ALogP 2.86, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): COc1cc2[nH]c(C(=O)NCCC3CCN(Cc4ccccc4)CC3)cc(=O)c2cc1OC
InChIKey: FYEQJLDNQJUZMM-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in baculovirus infected BTI insect cells using p-tyramine as substrate pretreated for 15 mins followed by substrate addition by horse-radish peroxidase/amplex red-based fluorescence method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 449.55, ALogP 3.58, HBA 5, HBD 2, PSA 83.66, QED 0.55