lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)C(F)(F)F)cccn3n2)on1
InChIKey: IRINTXPZAZNXNO-YWVIFJGQSA-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 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 472.42, ALogP 3.93, HBA 8, HBD 1, PSA 80.72, QED 0.54
Compound (SMILES): CCn1oc2cc(-c3c(C)nc4c(OCc5ccc(-c6ccc(F)cc6)cc5)cccn34)ccc2c1=O.Cl
InChIKey: IMNXEHRVZLTILV-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Inhibition of gamma-secretase in human SK-N-BE cells assessed as decrease in amyloid beta 42 production treated for 6 hrs by ELISA
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 493.54, ALogP 6.62, HBA 6, HBD 0, PSA 61.67, QED 0.26
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(F)c(F)c2)ncn1
InChIKey: FRKVPKQQZQNZHG-FIOXXRHOSA-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 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 465.55, ALogP 4.3, HBA 7, HBD 1, PSA 71.76, QED 0.62
Compound (SMILES): Cc1nnc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OC(C)C(F)(F)F)ccc(C(F)(F)F)n3n2)o1
InChIKey: PPZKUFDGGKRNJA-LBDWZGLVSA-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 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 505.42, ALogP 4.1, HBA 9, HBD 1, PSA 93.61, QED 0.52
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2cc(F)cc(F)c2)ncn1
InChIKey: AXUCGPSYXKJACT-VPTLXERWSA-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 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 452.51, ALogP 3.52, HBA 8, HBD 1, PSA 75, QED 0.65
Compound (SMILES): CCn1c(=O)c2ccc(-c3c(C)nc4c(OCc5ccc(-c6ccc(F)cc6)cc5)cccn34)cc2n1C.Cl
InChIKey: GOGSALYLGFAFHZ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Inhibition of gamma-secretase in human SK-N-BE cells assessed as decrease in amyloid beta 42 production treated for 6 hrs by ELISA
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 506.58, ALogP 6.37, HBA 6, HBD 0, PSA 53.46, QED 0.26
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccc(-n5cncn5)cc4)cccn23)cn1.Cl
InChIKey: IRTCQYBEAOCPCH-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 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 453.51, ALogP 3.61, HBA 8, HBD 1, PSA 99.23, QED 0.4
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCN3c2ccc(C(F)(F)F)cc2)ncn1
InChIKey: ZARAJXPSYXIZAY-CWPLJXCYSA-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 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 470.5, ALogP 3.87, HBA 8, HBD 1, PSA 75, QED 0.62
Compound (SMILES): Fc1ccc(C2CCCCn3nc(N[C@@H]4[C@@H]5CC[C@H]4CN(c4cnnc(Cl)c4)C5)nc32)c(F)c1F
InChIKey: GUQVVVPFTFBSKS-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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 503.96, ALogP 4.78, HBA 7, HBD 1, PSA 71.76, QED 0.52
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCC[C@H]3c2ccc(F)c(F)c2F)ncn1
InChIKey: XGTZKVXMDSWEOE-FIEAQMJYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of human gamma secretase expressed in HEK293 cells assessed as reduction in total amyloid beta (1 to 42 residues) production
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 483.54, ALogP 4.44, HBA 7, HBD 1, PSA 71.76, QED 0.55
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2cc(F)cc(F)c2)ncn1
InChIKey: AXUCGPSYXKJACT-VPTLXERWSA-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 free amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 452.51, ALogP 3.52, HBA 8, HBD 1, PSA 75, QED 0.65
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCC[C@H]3c2ccc(F)c(F)c2F)ncn1
InChIKey: XGTZKVXMDSWEOE-FIEAQMJYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of human gamma secretase expressed in HEK293 cells assessed as reduction in free amyloid beta (1 to 42 residues) production
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 483.54, ALogP 4.44, HBA 7, HBD 1, PSA 71.76, QED 0.55
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2cc(F)cc(F)c2)ncn1
InChIKey: AXUCGPSYXKJACT-VPTLXERWSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of human gamma secretase expressed in HEK293 cells assessed as reduction in total amyloid beta (1 to 42 residues) production
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 452.51, ALogP 3.52, HBA 8, HBD 1, PSA 75, QED 0.65
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2cc(F)cc(F)c2)ncn1
InChIKey: AXUCGPSYXKJACT-VPTLXERWSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of human gamma secretase expressed in HEK293 cells assessed as reduction in free amyloid beta (1 to 42 residues) production
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 452.51, ALogP 3.52, HBA 8, HBD 1, PSA 75, QED 0.65
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2ccc(F)c(F)c2)ncn1
InChIKey: AKMITMDHRFFGLB-VPTLXERWSA-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 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 452.51, ALogP 3.52, HBA 8, HBD 1, PSA 75, QED 0.65
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4cccc(F)c4)cccn23)cn1.Cl
InChIKey: FPSSVQYWGJKCCD-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 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 404.45, ALogP 4.17, HBA 5, HBD 1, PSA 68.52, QED 0.52
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCC[C@H]3c2ccc(F)c(F)c2F)ncn1
InChIKey: XGTZKVXMDSWEOE-FIEAQMJYSA-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 free amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 483.54, ALogP 4.44, HBA 7, HBD 1, PSA 71.76, QED 0.55
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccc(-c5ccc(F)cc5)cc4)cccn23)cn1.Cl
InChIKey: DOPRKNQCKUHFSE-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Inhibition of gamma-secretase in human SK-N-BE cells assessed as decrease in amyloid beta 42 production treated for 6 hrs by ELISA
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 480.54, ALogP 5.84, HBA 5, HBD 1, PSA 68.52, QED 0.32
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCC3c2ccc(C(F)(F)F)cc2)ncn1
InChIKey: ZDWOQGBIAXVXGV-VPFIRPQJSA-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 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 483.54, ALogP 4.65, HBA 7, HBD 1, PSA 71.76, QED 0.58
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(F)c(F)c2F)on1
InChIKey: MMZQCMROZVIPNU-SYHBATSHSA-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 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 472.52, ALogP 4.63, HBA 7, HBD 1, PSA 72.01, QED 0.56
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4cccc(-c5ccccc5)c4)cccn23)cn1.Cl
InChIKey: JBEAXIJKERIYMF-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 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 462.55, ALogP 5.7, HBA 5, HBD 1, PSA 68.52, QED 0.34
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)C(F)(F)F)cccn3n2)on1
InChIKey: IRINTXPZAZNXNO-YWVIFJGQSA-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 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 472.42, ALogP 3.93, HBA 8, HBD 1, PSA 80.72, QED 0.54
Compound (SMILES): CCn1oc2cc(-c3c(C)nc4c(OCc5ccc(-c6ccc(F)cc6)cc5)cccn34)ccc2c1=O.Cl
InChIKey: IMNXEHRVZLTILV-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Inhibition of gamma-secretase in human SK-N-BE cells assessed as decrease in amyloid beta 42 production treated for 6 hrs by ELISA
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 493.54, ALogP 6.62, HBA 6, HBD 0, PSA 61.67, QED 0.26
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCCC3c2ccc(F)c(F)c2)ncn1
InChIKey: FRKVPKQQZQNZHG-FIOXXRHOSA-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 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 465.55, ALogP 4.3, HBA 7, HBD 1, PSA 71.76, QED 0.62
Compound (SMILES): Cc1nnc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OC(C)C(F)(F)F)ccc(C(F)(F)F)n3n2)o1
InChIKey: PPZKUFDGGKRNJA-LBDWZGLVSA-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 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 505.42, ALogP 4.1, HBA 9, HBD 1, PSA 93.61, QED 0.52
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2cc(F)cc(F)c2)ncn1
InChIKey: AXUCGPSYXKJACT-VPTLXERWSA-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 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 452.51, ALogP 3.52, HBA 8, HBD 1, PSA 75, QED 0.65
Compound (SMILES): CCn1c(=O)c2ccc(-c3c(C)nc4c(OCc5ccc(-c6ccc(F)cc6)cc5)cccn34)cc2n1C.Cl
InChIKey: GOGSALYLGFAFHZ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Inhibition of gamma-secretase in human SK-N-BE cells assessed as decrease in amyloid beta 42 production treated for 6 hrs by ELISA
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 506.58, ALogP 6.37, HBA 6, HBD 0, PSA 53.46, QED 0.26
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccc(-n5cncn5)cc4)cccn23)cn1.Cl
InChIKey: IRTCQYBEAOCPCH-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 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 453.51, ALogP 3.61, HBA 8, HBD 1, PSA 99.23, QED 0.4
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCN3c2ccc(C(F)(F)F)cc2)ncn1
InChIKey: ZARAJXPSYXIZAY-CWPLJXCYSA-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 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 470.5, ALogP 3.87, HBA 8, HBD 1, PSA 75, QED 0.62
Compound (SMILES): Fc1ccc(C2CCCCn3nc(N[C@@H]4[C@@H]5CC[C@H]4CN(c4cnnc(Cl)c4)C5)nc32)c(F)c1F
InChIKey: GUQVVVPFTFBSKS-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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 503.96, ALogP 4.78, HBA 7, HBD 1, PSA 71.76, QED 0.52
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCC[C@H]3c2ccc(F)c(F)c2F)ncn1
InChIKey: XGTZKVXMDSWEOE-FIEAQMJYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of human gamma secretase expressed in HEK293 cells assessed as reduction in total amyloid beta (1 to 42 residues) production
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 483.54, ALogP 4.44, HBA 7, HBD 1, PSA 71.76, QED 0.55
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2cc(F)cc(F)c2)ncn1
InChIKey: AXUCGPSYXKJACT-VPTLXERWSA-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 free amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 452.51, ALogP 3.52, HBA 8, HBD 1, PSA 75, QED 0.65
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCC[C@H]3c2ccc(F)c(F)c2F)ncn1
InChIKey: XGTZKVXMDSWEOE-FIEAQMJYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of human gamma secretase expressed in HEK293 cells assessed as reduction in free amyloid beta (1 to 42 residues) production
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 483.54, ALogP 4.44, HBA 7, HBD 1, PSA 71.76, QED 0.55
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2cc(F)cc(F)c2)ncn1
InChIKey: AXUCGPSYXKJACT-VPTLXERWSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of human gamma secretase expressed in HEK293 cells assessed as reduction in total amyloid beta (1 to 42 residues) production
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 452.51, ALogP 3.52, HBA 8, HBD 1, PSA 75, QED 0.65
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2cc(F)cc(F)c2)ncn1
InChIKey: AXUCGPSYXKJACT-VPTLXERWSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of human gamma secretase expressed in HEK293 cells assessed as reduction in free amyloid beta (1 to 42 residues) production
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 452.51, ALogP 3.52, HBA 8, HBD 1, PSA 75, QED 0.65
Compound (SMILES): CCC(CC)[C@H](NC(C)=O)[C@@H]1[C@H](OC(=O)NCCCOC(=O)/C=C/c2ccc(O)c(O)c2)[C@@H](C(=O)O)C[C@H]1NC(=N)N
InChIKey: DOIYAGBAFZCYFH-KWKBSNTCSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: A5Z252
Assay: Inhibition of Influenza A virus (A/Vietnam/1194/2004 (H5N1)) recombinant neuraminidase expressed in HEK293 cells pre-incubated for 10 mins before 4-MUNANA substrate addition by fluorometry
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 591.66, ALogP 1.65, HBA 9, HBD 8, PSA 233.39, QED 0.04
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(Cl)c(OCc3ccc(F)cc3)c2)c1
InChIKey: YALQAUZSXADMLL-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 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-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B 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 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 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 < 100 nM (pChEMBL 7)
Descriptors: MW 453.86, ALogP 4.92, HBA 6, HBD 1, PSA 86.47, QED 0.41
Compound (SMILES): CC(=O)NCC(=O)N1[C@@H]2CC[C@H]1c1ccc(Nc3ncc(C(F)(F)F)c(NC4CCC4)n3)cc12
InChIKey: RYYNGWLOYLRZLK-RBUKOAKNSA-N
Target: Acyl-CoA dehydrogenase family member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q709F0
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 474.49, ALogP 4.06, HBA 6, HBD 3, PSA 99.25, QED 0.58
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: RURUHDYEMBKXIP-DVIQCWQXSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y1R expressed in BHK-21 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 4036.49
Compound (SMILES): O=C(O)C1CCCN(C/C=C/C(c2ccc3c(c2)OCO3)(c2ccc3c(c2)OCO3)c2ccc3c(c2)OCO3)C1
InChIKey: WEIMTPANZVJKSW-WTDSWWLTSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by liquid scintillation counting method
Measurement: IC50 = 15135.61 nM (pChEMBL 4.820000171661377)
Descriptors: MW 543.57, ALogP 4.56, HBA 8, HBD 1, PSA 95.92, QED 0.34
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCC3CCCCC3)cn2)c1
InChIKey: JJIYEQBZHWJIEX-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 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-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A 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 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 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 < 100 nM (pChEMBL 7)
Descriptors: MW 299.37, ALogP 3.61, HBA 4, HBD 1, PSA 68.01, QED 0.92
Compound (SMILES): CC(C)C(c1ccccc1)n1cnc(-c2cc(-c3nn[nH]n3)ccn2)c1
InChIKey: RNHDGJROFDMRJA-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 345.41, ALogP 3.37, HBA 6, HBD 1, PSA 85.17, QED 0.6
Compound (SMILES): CN(C)CCCOc1cccc(/C=C2\COc3ccccc3C2=O)c1
InChIKey: DKAZPBKVFIJMAG-GHRIWEEISA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured at 1 to 3 mins time interval by Ellman's method
Measurement: IC50 = 25720 nM (pChEMBL 4.590000152587891)
Descriptors: MW 337.42, ALogP 3.68, HBA 4, HBD 0, PSA 38.77, QED 0.6
Compound (SMILES): COc1ccc2ccc3c(c2c1)C(CNC(N)=S)CC3
InChIKey: HWMXBPNNULQCOI-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 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 286.4, ALogP 2.71, HBA 2, HBD 2, PSA 47.28, QED 0.85
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCNCc3ccccc3Cl)cn2)c1
InChIKey: HXFAEJNSXYWOET-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 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-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A 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 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 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 < 100 nM (pChEMBL 7)
Descriptors: MW 356.81, ALogP 3.09, HBA 5, HBD 2, PSA 80.04, QED 0.64
Compound (SMILES): Fc1c(Cn2cnc(-c3cc(-c4c[nH]nn4)ccn3)c2)cccc1OC(F)(F)F
InChIKey: NZTCCZUHIHSENS-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: PHF8 Assay: The ability of test compounds to inhibit the activity of PHF8 was determined in 384-well plate format under the following reaction conditions: 3 nM PHF8, 200 nM H3K9me1-biotin labeled peptide (Anaspec cat #64358), 0.5 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 5 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-unmodified-histone H3 lysine 9/lysine27 (H3K9/K27) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 0.5 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 600 nM H3K9me1-biotin labeled peptide and 1.5 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 9 nM PHF8 to initiate the reaction. The reaction mixture was incubated at rt for 15 min, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 1 nM Europium-anti-unmodified H3K9/K27 antibody. Plates were read by EnVision Multilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hr incubation at rt. 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 404.33, ALogP 3.82, HBA 6, HBD 1, PSA 81.51, QED 0.51
Compound (SMILES): N#Cc1cc(Nc2cc(NC3CC3)c3ncc(C(N)=O)n3n2)cc(C(F)(F)F)c1
InChIKey: LZDFDVIPCRRLMW-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 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 401.35, ALogP 3.04, HBA 7, HBD 3, PSA 121.13, QED 0.6
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCN3CCCc4ccccc43)cn2)c1
InChIKey: XSSUXYYELFOOBB-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 348.41, ALogP 3.1, HBA 5, HBD 1, PSA 71.25, QED 0.77
Compound (SMILES): C[C@@H](Nc1nc(NC(=O)c2ccccc2)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: IQRLKQDCDTZTJN-GFCCVEGCSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C) Inhibitors: A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 428.42, ALogP 4.42, HBA 6, HBD 2, PSA 92.69, QED 0.6
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(F)c(F)c2)c1
InChIKey: GMWKOCOYZWNSIJ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 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-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B 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 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 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 < 100 nM (pChEMBL 7)
Descriptors: MW 331.28, ALogP 2.82, HBA 5, HBD 1, PSA 77.24, QED 0.78
Compound (SMILES): COc1ccc(C(/C=C/CN2CCC[C@H](C(=O)O)C2)(c2ccc(OC)cc2)c2ccc3sccc3c2)cc1
InChIKey: BCLUMDBGGSYAHR-UZJKPBDZSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by liquid scintillation counting method
Measurement: IC50 = 2884.03 nM (pChEMBL 5.539999961853027)
Descriptors: MW 527.69, ALogP 6.61, HBA 5, HBD 1, PSA 59, QED 0.2
Compound (SMILES): FC(F)(F)c1[nH]nnc1-c1ccnc(-c2cn(CC3CCc4ccccc43)cn2)c1
InChIKey: JAGKRJVLUACVQE-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 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, and 2 uM 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-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 410.4, ALogP 4.48, HBA 5, HBD 1, PSA 72.28, QED 0.54
Compound (SMILES): CCc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@@H]3C(=O)N(CC)C(=O)N23)o1
InChIKey: VKKJMPZSQBNIOL-VQIMIIECSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of full length recombinant human N-terminal GST-tagged PDE4A1A expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 363.42, ALogP 3.62, HBA 3, HBD 1, PSA 69.55, QED 0.72
Compound (SMILES): CCn1cc(C2CCN(C(=O)C3CCCC3)CC2)c2cc(NC(=O)c3cc(C#N)ccn3)ccc21
InChIKey: HGQGBGOXODGAQZ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Displacement of [3H]-25-hydroxycholesterol from human N-terminal 6His-tagged-RORC2 LBD (259 to 483 residues) expressed in Escherichia coli (DE3) cells by scintillation proximity assay
Measurement: Ki = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 469.59, ALogP 5.08, HBA 5, HBD 1, PSA 91.02, QED 0.56
Compound (SMILES): FC1(F)CC(Nc2nc(NC3CC(F)(F)C3)nc(-c3cncc(C(F)(F)F)n3)n2)C1
InChIKey: BJUUMSAHTGGBTK-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 437.32, ALogP 3.77, HBA 7, HBD 2, PSA 88.51, QED 0.69
Compound (SMILES): O=C(O)c1ccc(N2CC3(CCN(Cc4cc(C(F)(F)F)ccc4C4CC4)CC3)OC2=O)cc1
InChIKey: UNCDRASKFWAOIZ-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 474.48, ALogP 5.27, HBA 4, HBD 1, PSA 70.08, QED 0.64
Compound (SMILES): CN1CC(=O)N2[C@H](c3ccc(Br)s3)c3[nH]c4ccccc4c3C[C@@H]2C1=O
InChIKey: KUYGOKWGSHFXJD-FZKQIMNGSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of full length recombinant human N-terminal GST-tagged PDE4A1A expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 430.33, ALogP 3.31, HBA 3, HBD 1, PSA 56.41, QED 0.64
Compound (SMILES): C[C@@H](Nc1nc(NC(C2CC2)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: IEWNKIUGPADRRO-LLVKDONJSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 6 hrs before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 418.47, ALogP 4.76, HBA 6, HBD 2, PSA 75.62, QED 0.64
Compound (SMILES): O=C(CCCN1CCC(c2noc3cc(F)ccc23)CC1)c1cc2c3c(c1)CCN3C(=O)CC2
InChIKey: LFATXWJLBURBCJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08909
Assay: Displacement of [3H]-mesulergine from serotonin 5-HT2C receptor in rat brain cerebral cortex homogenates incubated for 15 mins by liquid scintillation counting
Measurement: Ki = 610.3 nM (pChEMBL 6.210000038146973)
Descriptors: MW 461.54, ALogP 4.64, HBA 5, HBD 0, PSA 66.65, QED 0.5
Compound (SMILES): N[C@H]1C[C@@H]1c1ccc(-c2cccc(O)c2)cc1
InChIKey: DSOJSZXQRJGBCW-CABCVRRESA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant LSD1 using dimethylated H3K4 peptide as substrate after 1 hr
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 225.29, ALogP 2.87, HBA 2, HBD 2, PSA 46.25, QED 0.83
Compound (SMILES): O=C(Nc1ccc(Oc2ccnc3[nH]ccc23)c(F)c1)c1cc2cccnc2n(-c2ccc(F)cc2)c1=O
InChIKey: IXULLLZCNUKGBJ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using poly(Glu, Tyr) 4:1 as substrate after 30 mins by HTRF assay
Measurement: IC50 = 632.8 nM (pChEMBL 6.199999809265137)
Descriptors: MW 509.47, ALogP 5.58, HBA 6, HBD 2, PSA 101.9, QED 0.32
Compound (SMILES): CC(=O)N1CCC(c2ccc3oc4nc(N)c(C(=O)O)cc4c(=O)c3c2)CC1
InChIKey: JLEKSULAPAVAGH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Kinase Assays: Kinase assays are commonly used for determining the ability of a small molecule to inhibit enzyme activity. By measuring the degree of phosphorylation of a substrate at varying concentrations of inhibitor, the concentration of inhibitor resulting in 50% enzymatic activity (IC50) can be obtained. The IC50 is defined as the inflection point of the sigmoidal graph obtained when plotting substrate phosphorylation vs. inhibitor concentration. Experiments were conducted during development of embodiments herein using radiolabeled ATP to detect substrate phosphorylation in the presence of amlexanox analogs to determine the potency (IC50) of said analogs.TBK1 (residues 1-657) and IKKε (residues 1-655) were purified from insect cells to ≥90% purity by coomassie staining. Reactions containing 50 nM TBK1 or IKKε, 7 μM myelin basic protein (MBP), and inhibitor in reaction buffer (50 mM HEPES pH 7.5, 10 mM NaCl, 10 mM MgCl2, 1 mM DTT) were initiated with 5 μM ATP spiked with [γ-32P]-ATP and allowed to proceed for 30 minutes at room temperature. Reactions were quenched with SDS gel loading dye, run on 4-15% SDS-PAGE gels, and imaged on phosphorimaging screens. Band intensities corresponding to phosphorylated MBP were quantified with ImageQuant and the data analyzed in Prism 6. Dose-response assay band intensities were normalized and fit to a sigmoidal dose-response equation with the Hill slope fixed at −1 and the top constrained to 100.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 381.39, ALogP 2.35, HBA 6, HBD 2, PSA 126.73, QED 0.65
Compound (SMILES): N#CC1(c2cc(Nc3nc(NCC(F)(F)F)nc(-c4cccc(Cl)n4)n3)ccn2)CC1
InChIKey: NQOVQEWIOBPOQW-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 446.82, ALogP 4.25, HBA 8, HBD 2, PSA 112.3, QED 0.54
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(C(C)(C)C(=O)Nc3ccc(F)cc3)cc2)cc1
InChIKey: KUBGKOCHEJNDBQ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35398
Assay: Displacement of [3H]T0901317 from recombinant human GST-fused RORalpha LBD after 1 to 4 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 482.58, ALogP 4.72, HBA 4, HBD 2, PSA 92.34, QED 0.49
Compound (SMILES): Fc1cccc(Cl)c1CCn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: QOOHLXDCOHAFJS-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 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 436.8, ALogP 4.78, HBA 5, HBD 1, PSA 72.28, QED 0.46
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cccc(Cl)n3)n2)CC1
InChIKey: UIBBMCJNFUASJY-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 458.89, ALogP 5.57, HBA 6, HBD 2, PSA 75.62, QED 0.45
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(Cl)cc2OCc2ccc(F)cc2)c1
InChIKey: WVEHUIVVPBXOJC-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 = 1000 nM (pChEMBL 6)
Descriptors: MW 453.86, ALogP 4.92, HBA 6, HBD 1, PSA 86.47, QED 0.41
Compound (SMILES): N#CC1(c2cc(Nc3nc(N[C@@H]4CCC(F)(F)C4)nc(-n4ccc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: WFGLMCWPQJGAJJ-CYBMUJFWSA-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 7.300000190734863)
Descriptors: MW 491.43, ALogP 4.37, HBA 9, HBD 2, PSA 117.23, QED 0.49
Compound (SMILES): N#Cc1cnc(NCc2ccccc2OC(F)(F)F)nc1NC[C@]12C[C@@H]3C[C@H](C1)[C@@H](NCCO)[C@@H](C3)C2
InChIKey: CIVFNZIOXQANAM-JSKUAUQASA-N
Target: Protein kinase C gamma type (SINGLE PROTEIN), Homo sapiens
UniProt: P05129
Assay: Inhibition of recombinant N-terminal GST-fused full-length human PKCgamma expressed in Baculovirus expression system using STK1-biotin as substrate after 1 hr in presence of ATP by TR-FRET analysis
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 516.57, ALogP 4.05, HBA 8, HBD 4, PSA 115.12, QED 0.37
Compound (SMILES): CC(Nc1nc(Nc2ccnc(C(F)(F)F)c2)nc(-n2ccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: ORPDRKJAHZEOLR-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 486.3, ALogP 4.6, HBA 8, HBD 2, PSA 93.44, QED 0.51