lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Agonist activity at human wild-type 5-HT7 receptor expressed in HEK cells assessed as cAMP by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Agonist activity at human wild-type A2A receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Agonist activity at human wild-type A2A receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Agonist activity at human wild-type A3 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Agonist activity at human wild-type A3 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Agonist activity at human wild-type alpha 1A receptor expressed in CHO cells assessed as calcium level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Agonist activity at human wild-type alpha 1A receptor expressed in CHO cells assessed as calcium level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Alpha-2A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08913
Assay: Agonist activity at human wild-type alpha 2A receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Alpha-2A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08913
Assay: Agonist activity at human wild-type alpha 2A receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Alpha-2C adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18825
Assay: Agonist activity at human wild-type alpha 2C receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Alpha-2C adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18825
Assay: Agonist activity at human wild-type alpha 2C receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Agonist activity at human wild-type AGTR1 receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Agonist activity at human wild-type AGTR1 receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human wild-type AVPR1A receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human wild-type AVPR1A receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Cholecystokinin receptor type A (SINGLE PROTEIN), Homo sapiens
UniProt: P32238
Assay: Agonist activity at human wild-type CCKA receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Cholecystokinin receptor type A (SINGLE PROTEIN), Homo sapiens
UniProt: P32238
Assay: Agonist activity at human wild-type CCKA receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Agonist activity at human wild-type M3 receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Agonist activity at human wild-type M3 receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Agonist activity at human wild-type M1 receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Agonist activity at human wild-type M1 receptor expressed in CHO-K1 cells assessed as calcium level by FDSS assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Agonist activity at human wild-type M2 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Agonist activity at human wild-type M2 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at human wild-type D1 receptor expressed in CHO cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at human wild-type D1 receptor expressed in CHO cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human wild-type D2 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human wild-type D2 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Endothelin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25101
Assay: Agonist activity at human wild-type ETA receptor expressed in CHO-K1 cells assessed as calcium level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Endothelin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25101
Assay: Agonist activity at human wild-type ETA receptor expressed in CHO-K1 cells assessed as calcium level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human wild-type opioid-delta 1 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human wild-type opioid-delta 1 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human wild-type opioid-kappa 1 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human wild-type opioid-kappa 1 receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human wild-type opioid-mu receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human wild-type opioid-mu receptor expressed in CHO-K1 cells assessed as cAMP level by HTRF assay
Measurement: EC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 by LC-MS analysis
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 by LC-MS analysis
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 by LC-MS analysis
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of human CYP2C8 by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of human CYP2C8 by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2cccc(OCC(O)CN(C)C)c2N1
InChIKey: CCSPGLLRANVKRG-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.15
Compound (SMILES): CB1C=Cc2c(cccc2OCC(O)CN(C)C)N1
InChIKey: KVVLFJLSBAOKPZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 260.15
Compound (SMILES): CC(C)n1nc(C#Cc2cccc(NC(=O)c3cccc(C(F)(F)F)c3)c2)c2c(N)ncnc21
InChIKey: NYUZAHPHSBKPPK-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of wild-type Bcr-Abl autophosphorylation (unknown origin) expressed in mouse BA/F3 cells for 3 hrs by Western blot analysis
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 464.45, ALogP 4.66, HBA 6, HBD 2, PSA 98.72, QED 0.43
Compound (SMILES): CC(C)n1nc(C#Cc2cccc(NC(=O)c3cccc(C(F)(F)F)c3)c2)c2c(N)ncnc21
InChIKey: NYUZAHPHSBKPPK-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of Bcr-Abl T315I mutant (unknown origin) autophosphorylation expressed in mouse BA/F3 cells for 3 hrs by Western blot analysis
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 464.45, ALogP 4.66, HBA 6, HBD 2, PSA 98.72, QED 0.43
Compound (SMILES): Nc1cc(F)ccc1NC(=O)CCCCCNC(=O)c1cccnc1
InChIKey: DYMGQCRVFMJSQR-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: HDAC enzyme inhibitionAssay: HDAC enzyme inhibition assays were performed using purified HDACs 1-10 essentially as described in Beckers et al., 2007, Int. J. Cancer., 121:1138-48 and Perez-Balado et al., 2007, J. Med. Chem., 50:2497-2505. Inhibition assays using nuclear extract were performed essentially as described in Herman et al., 2006, Nat. Chem. Biol., 2:551-558. Briefly, the purified HDACs or nuclear extract were incubated with an acetylated substrate in the absence of the compound to be assayed and with increasing concentrations of the compound. The rate of substrate deacetylation was measured under each condition, and half-maximal inhibitory concentration with regard to each HDAC was determined by standard means.
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 344.39, ALogP 2.73, HBA 4, HBD 3, PSA 97.11, QED 0.51
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)NCCCC[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1)C(=O)O
InChIKey: JPDRWIFETVDWOH-PMWIVKDASA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Agonist activity at HA-tagged human CXCR4 receptor expressed in HEK293 cells co-transfected with Galphai1-91-RlucII, Gbeta1, and GFP10-G-gamma1 incubated for 7 mins by Galpha1 protein activation-based BRET assay
Measurement: EC50 = 152 nM (pChEMBL 6.820000171661377)
Descriptors: MW 3195.83
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CSCNC(C)=O)NC(=O)[C@H](CO)NC(=O)CN(C)C)C(C)C)C(N)=O
InChIKey: XNRHGZCDDKNHLQ-LOBNYJLJSA-N
Target: Neuromedin-B receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P24053
Assay: Displacement of [125I]-NMB from NMB receptor in rat C6 cells
Measurement: IC50 = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 1517.76
Compound (SMILES): CCOc1cc(=O)n(C)cc1-c1cc(NCc2ccc(F)cc2)ccc1Oc1ccc(F)cc1F
InChIKey: YVUKZBQRWODYJF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Assay method C: Compound dilution series were prepared in DMSO via an approximately 3-fold serial dilution from one of the following: 0.047 mM to 0.78 nM or 5-fold serial dilution from Assay method A. Compound dilutions were added directly into white, low-volume assay plates (Perkin Elmer Proxiplate 384 Plus# 6008280) using a Labcyte Echo in conjunction with Labcyte Access and Thermo Multidrop CombinL robotics. Compounds were then suspended in eight microliters (μL) of assay buffer (20 mM Sodium Phosphate, pH 6.0, 50 mM NaCl, 1 mM Ethylenediaminetetraacetic acid disodium salt dihydrate, 0.01% Triton X-100, 1 mM DL-Dithiothreitol) containing His-tagged bromodomain, Europium-conjugated anti-His antibody (Invitrogen PV5596) and Alexa-647-conjugated probe. The final concentration of 1X assay mixture for assay methods A, B and C contains 2% DMSO, 8 nM His-tagged bromodomain, 1 nM Europium-conjugated anti-His-tag antibody and 100 nM or 30 nM probe (for BDI or BDII, respectively) and compound concentration in the range of: 49.02 μM-15.63 nM for method A, 9.19 μM 150 pM for method B, and 0.92 μM 15 pM for method C. After a one-hour equilibration at room temperature, TR-FRET ratios were determined using an Envision multilabel plate reader (Ex 340, Em 495/520).
Measurement: Ki = 61.8 nM (pChEMBL 7.210000038146973)
Descriptors: MW 480.49, ALogP 6.27, HBA 5, HBD 1, PSA 52.49, QED 0.32
Compound (SMILES): COC(C)COC(=O)N1CCC(CC#N)(n2cc(C(N)=O)c(Nc3ccc(F)cc3)n2)CC1
InChIKey: CDQHKCCFKUGSMZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Biochemical Assay: The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at room temperature for 120 minutes. At the end of the incubation, 20 uL of 2x stop buffer (streptavidin-Dylight 650 (Thermo #84547B/100 mL), Eu-tagged pY20 antibody (Perkin Elmer #AD0067), EDTA, HEPES, and Triton) was added to quench the reaction.
Measurement: IC50 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 458.49, ALogP 2.74, HBA 8, HBD 2, PSA 135.5, QED 0.62
Compound (SMILES): Cn1cc(-c2cc(NS(C)(=O)=O)ccc2Oc2ccc(F)cc2F)c2cc[nH]c2c1=O
InChIKey: AKWTUXWXJYRCCZ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Bromodomain Domain Binding Assay: A time-resolved fluorescence resonance energy transfer (TR-FRET) assay was used to determine the affinities of compounds of the Examples listed in Table 1 for each bromodomain of human BRD4. His-tagged first (BD1: amino acids K57-E168) and second (BD2: amino acids E352-E168) bromodomains of human BRD4 were expressed and purified. An Alexa647-labeled BET-inhibitor was used as the fluorescent probe in the assay. Compound dilution series were prepared in DMSO via a 3-fold serial dilution from 2.5 mM to 42 nM. Compounds were then diluted 6:100 in assay buffer (20 mM Sodium Phosphate, pH 6.0, 50 mM NaCl, 1 mM Ethylenediaminetetraacetic acid disodium salt dihydrate, 0.01% Triton X-100, 1 mM DL-Dithiothreitol) to yield 3× working solutions. Six microliters (L) of the working solution was then transferred to white, low-volume assay plates (Costar #3673). A 1.5× assay mixture containing His-tagged bromodomain, Europium-conjugated anti-His antibody (Invitrogen PV5596) and the Alexa-647-conjugated probe molecule was also prepared. Twelve L of this solution were added to the assay plate to reach a final volume of 18 L. The final concentration of 1× assay buffer contains 2% DMSO, 50 M-0.85 nM compound, 8 nM His-tagged bromodomain, 1 nM Europium-conjugated anti-His-tag antibody and 100 nM or 30 nM probe (for BDI or BDII, respectively). After a one-hour incubation at room temperature, TR-FRET ratios were determined using an Envision multilabel plate reader (Ex 340, Em 495/520).
Measurement: Ki = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 445.45, ALogP 3.98, HBA 5, HBD 2, PSA 93.19, QED 0.49
Compound (SMILES): Cc1cc(-c2cn(CCNCC(C)C)c(C3CCN(c4ncnc(N)c4C(N)=O)CC3)n2)ccc1F
InChIKey: DPTJVGTULVNDHT-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: AKT Enzyme Assay: A TTP Mosquito liquid handling instrument is used to place 125 nl of the appropriate concentration of inhibitor in 100% DMSO (for a dose response curve calculation) into each well of a 384-well plate. To this reaction components are added to a final volume of 12.5 .mu.l: 0.1 ng/.mu.l His-AKT (Full Length), (Invitrogen, Part # P2999, Lot #641228C). 160 uM ATP (Fluka, 02055) 1 mM DTT (Sigma, D0632) 1 mM MgCl2 (Sigma, M1028) 1 .mu.M substrate peptide (sequence FITC-AHA-GRPRTSSFAEG-NH2), synthesized by Tufts Peptide Synthesis service. 100 mM HEPES pH 7.5 (Calbiochem, 391338)0.015% Brij-35 (Sigma, B4184)The reaction is incubated for 90 min at 25 C, and then stopped by the addition of 70 .mu.l of Stop buffer (100 mM HEPES pH 7.5, 0.015% Brij-35, 10 mM EDTA (Sigma, E7889)).The plate is read on a Caliper LC 3000 in an Off-Chip mobility shift assay format, using the following parameters for a 12-sipper chip: screening pressure -2.3 psi, upstream voltage -500, and downstream voltage -3000.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 494.62, ALogP 3.1, HBA 8, HBD 3, PSA 127.98, QED 0.39
Compound (SMILES): Cc1c(C(=O)N2CCC3(CC2)CC3CNC(=O)N2Cc3ccncc3C2)cnn1C
InChIKey: CWEANAMMJQOLMQ-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 408.51, ALogP 2.09, HBA 5, HBD 1, PSA 83.36, QED 0.84
Compound (SMILES): COc1ccc(C2(OCCCCn3cnc(CC(=O)O)c3)c3ccccc3-c3ccccc32)cc1
InChIKey: OUHDVVXKLISLQQ-UHFFFAOYSA-N
Target: GABA transporter 2 (SINGLE PROTEIN), Mus musculus
UniProt: P31651
Assay: Inhibition of mouse GAT2 expressed in HEK293 cells assessed as decrease in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition measured after 10 mins by liquid scintillation counter method
Measurement: IC50 = 23988.33 nM (pChEMBL 4.619999885559082)
Descriptors: MW 468.55, ALogP 5.29, HBA 5, HBD 1, PSA 73.58, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccc(N)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PDRZSJXTKWJVHW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 491.56, ALogP 4.21, HBA 9, HBD 1, PSA 104.21, QED 0.35
Compound (SMILES): NC(=O)[C@H](CC1CC1)NC(=O)c1ccc(N2CC(F)(F)C2)c(OCC2CC2)n1
InChIKey: OMJKDKUDNPHJGY-AWEZNQCLSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: cAMP Assay: CHO cells expressing human CB1 or CB2 receptors are seeded 17-24 hours prior to the experiment 50.000 cells per well in a black 96 well plate with flat clear bottom (Corning Costar #3904) in DMEM (Invitrogen No. 31331), 1.times.HT supplement, with 10% fetal calf serum and incubated at 5% CO2 and 37° C. in a humidified incubator. The growth medium was exchanged with Krebs Ringer Bicarbonate buffer with 1 mM IBMX and incubated at 30.degree. C. for 30 min Compounds were added to a final assay volume of 100 ul and incubated for 30 min at 30° C. Using the cAMP-Nano-TRF detection kit the assay (Roche Diagnostics) was stopped by the addition of 50 ul lysis reagent (Tris, NaCl, 1.5% Triton X100, 2.5% NP40, 10% NaN.sub.3) and 50 ul detection solutions (20 uM mAb Alexa700-cAMP 1:1, and 48 uM Ruthenium-2-AHA-cAMP) and shaken for 2 h at room temperature. The time-resolved energy transfer is measured by a TRF reader (Evotec Technologies GmbH), equipped with a ND:YAG laser as excitation source. The plate is measured twice with the excitation at 355 nm and at the emission with a delay of 100 ns and a gate of 100 ns, total exposure time 10 s at 730 (bandwidth 30 nm) or 645 nm (bandwidth 75 nm), respectively. The FRET signal is calculated.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 394.42, ALogP 1.71, HBA 5, HBD 2, PSA 97.55, QED 0.66
Compound (SMILES): Cc1ccc2ncccc2c1-c1cc(-c2c(C)noc2C)cc2[nH]c(C(O)CCO)nc12
InChIKey: YBSGFKSXLCHYRE-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Homogeneous Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Binding of the two tandem bromodomains, BRD4-1 and BRD4-2, to an acetylated histone H4 peptide was measured using a homogeneous time resolved fluorescence resonance energy transfer (TR-FRET) assay. The synthetic peptide containing amino acids 1-18 of histone H4 was acetylated at lysine 5, 8, 12, 16 and conjugated to biotin (SGRGACKGGACKGLGACKGGAACKRH-GSGSK-biotin[SEQ ID NO:1]) was purchased from Millipore. BRD4-1 and BRD4-2 were expressed and purified from Escherichia coli as N-terminal His6-tagged proteins. An XL665 labeled anti-His antibody (Cisbio) was used to specifically bind BRD4 and a cryptate labeled streptavidin protein was used because it specifically recognized the biotinylated H4 peptide. Binding of BRD4 to the peptide resulted in an increase in FRET signal whereas disruption of this protein-peptide interaction with a small molecule inhibitor resulted in a decrease in FRET signal. Assays were performed in 50 mM Hepes (pH 7.5), 150 mM NaCl, 0.1 mg/ml BSA, 0.01% (v/v) Brij, 0.5% (v/v) DMSO and 200 nM H4 peptide at the following concentrations for each BRD4 isoform: 60 nM BRD4-1 and 120 nM BRD4-2. After an assay reaction time of 60 minutes at 25° C., binding was measured with 2 nM crytptate labeled streptavidin and 10 nM anti-His-XL665 antibody. TR-FRET signal was detected on an Envision plate reader (Ex: 320 nm; Em: 615/665 nm; 100 As delay and 200 Î¼s read window). Data were normalized based on a positive (2 Î¼M I-BET) and negative (DMSO) controls and IC50values were calculated from the fit of the dose-response curves to a four-parameter equation. All IC50 values represent geometric mean values of a minimum of four determinations.
Measurement: IC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 428.49, ALogP 4.77, HBA 6, HBD 3, PSA 108.06, QED 0.37
Compound (SMILES): COc1cc(/C=N/NC(=O)CCn2cc(C)c3c(C)cccc32)ccc1OCc1ccccn1
InChIKey: FAEYHKQWPWAMSA-MUFRIFMGSA-N
Target: Transient receptor potential cation channel subfamily M member 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZQ8
Assay: Inhibition of human TRPM5 transfected in HEK293 cells assessed as inhibition of KCl-stimulated membrane potential by FLIPR assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 456.55, ALogP 4.78, HBA 6, HBD 1, PSA 77.74, QED 0.29
Compound (SMILES): O=C(C[C@H]1CC[C@@H](c2nnn3cnc4[nH]ccc4c23)CC1)NCC(F)(F)F
InChIKey: NKVFBGZJEKEROP-PHIMTYICSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 380.37, ALogP 2.95, HBA 5, HBD 2, PSA 87.97, QED 0.73
Compound (SMILES): O=c1cc(C2=CCN(S(=O)(=O)C(F)(F)F)CC2)c2cc(C(c3ccc(Cl)cc3)c3ccc(Cl)cc3)ccc2[nH]1
InChIKey: GCQHNGDEXOHPKU-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: cAMP Assay: The following mixtures and buffer solutions were prepared: (a) Buffer 1: HBSS (Mediatech Cat#21-023-CV) with 5 mM HEPES (1 mM stock, Gibco BRL Cat#15630-056) and 0.1% BSA (7.5% stock, Invitrogen Cat#15260-037); (b) Buffer 2: 0.5 mM IBMX (200 mM stock in DMSO, Sigma 15879) in Buffer 1; (c) 1 uM cAMP Standard (50 uM stock, Perkin Elmer Cat# AD0262) diluted in Buffer 2 and serially diluted in Buffer 2, 12 doses at 1/2 dilutions resulting in a dose range of 1 uM to 0.5 nM; (d) d2 labelled cAMP (CisBio HTRF Detection Kit Cat #62AM4PEB reconstituted with 6 ml dH2O) diluted 1/20 with lysis buffer (CisBio HTRF Detection Kit Cat #62AM4PEB); (e) anti-cAMP (CisBio HTRF Detection Kit Cat #62AM4PEB reconstituted with 5 ml dH2O) diluted 1/20 with lysis buffer (CisBio HTRF Detection Kit Cat #62AM4PEB); and (f) Forskolin (Sigma Cat# F6886, 10 mM in DMSO) diluted first in DMSO to 1 mM and then to 1.5 uM in Buffer 2.
Measurement: EC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 593.45, ALogP 6.95, HBA 3, HBD 1, PSA 70.24, QED 0.25
Compound (SMILES): CO[C@@]12C=C[C@]3(C[C@@]1(C)[C@@H](O)c1ccc(F)cc1)[C@@H]1Cc4ccc(O)c5c4[C@]3(CCN1CC1CC1)[C@@H]2O5
InChIKey: FZDIMXLFHUBMEZ-KHRRJGGGSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Ligand Binding Assay: As Alt et al., 2002. Membranes (20 μg) are incubated in 50 mM Tris-HCl, pH 7.4 with [3H]diprenorphine or [3H]nociceptin in the absence or presence of varying concentrations of test compounds for 60 min in a shaking water bath at 25° C. Nonspecific binding is measured using 10 μM naloxone (MOR, DOR, KOR) or N/OFQ (NOP). Samples are filtered through GF/C glass-fiber filtermats mounted on a Brandel cell harvester and rinsed four times with 4° C. 50 mM Tris-HCl, pH 7.4 buffer. Filtermats are dried and 0.1 ml EcoLume scintillation cocktail added to each sample area to soak the filter. Each filtermat in a heat-sealed bag, is counted in a Wallac 1450 MicroBeta Liquid Scintillation and Luminescence Counter.
Measurement: Ki = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 503.61, ALogP 4.66, HBA 5, HBD 2, PSA 62.16, QED 0.58
Compound (SMILES): CN[C@@H](C)C(=O)Nc1ccc(-c2c(-c3cccnc3OC)nc3cc(Cl)ccn23)c(C#Cc2ccc3c(C)nccc3c2)n1
InChIKey: KUALBBKNPXFGDB-NRFANRHFSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Binding Assays (DELFIA): BIR3 domains (10 nM) were incubated with SMAC peptide (10 nM) in assay buffer (50 mM Tris, 120 mM NaCl, 0.1% BSA, 1 mM DTT, 0.05% Triton X100) for one hour at room temperature in the presence of inhibitory compounds. The assay mixture was transferred to a streptavidin coated plate and incubated for one hour at room temperature to allow binding of the biotinylated peptide and associated BIR3 domains to the plate. After several washing steps Eu labeled anti-GST antibody (e.g. Perkin Elmer DELFIA Eu-N1-antiGST AD0250) was added to detect BIR3 domain-SMAC peptide interactions according to Perkin Elmer's instructions. Briefly, the antibody was added (dilution 1:5000 in Perkin Elmer DELFIA Assay Buffer 2013-01) and incubated for one hour. After 3 washing steps using Delfia Washing Buffer (Perkin Elmer DELFIA Wash 2013-05), Enhancement Solution (Perkin Elmer Enhancement Asolution 2013-02) was added and incubation continued for 10 minutes.
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 602.1, ALogP 5.92, HBA 8, HBD 2, PSA 106.33, QED 0.23
Compound (SMILES): N[C@@H](CC(=O)N1CCN(c2nc(N3CCOCC3)nc(-n3c(C(F)F)nc4ccccc43)n2)CC1)c1ccccc1
InChIKey: UXQAGPOOUBBLKL-FQEVSTJZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) expressed in Escherichia coli-infected fall armyworm sf21 cells co-expressing p85 by kinase-glo luminescence assay
Measurement: IC50 = 1797 nM (pChEMBL 5.75)
Descriptors: MW 563.61, ALogP 2.72, HBA 10, HBD 1, PSA 118.53, QED 0.36
Compound (SMILES): C[C@H](Nc1ncc(F)c(N2C(=O)OC[C@@H]2[C@@H](C)O)n1)c1ncc(Cl)cc1Cl
InChIKey: DWCICAAUBMNBFX-JOAULVNJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: LC-MS Detection of 2-HG Assay: The biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Costar, Cat. No. 781201) using a final reaction volume of 30 μL and the following assay buffer conditions: 50 mM HEPES pH 7.4, 10 mM MgCl2, 50 mM KCl, 1 mM DTT, 0.02% BSA, 5 uM NADPH and 100 uM alpha-KG. The final reaction mixture contained 3.3% DMSO and inhibitors with concentrations ranging 0.02-50 μM. The IDH1 enzyme was used at a final concentration of 0.25 nM. Following 45 minutes incubation, the reaction mixtures were quenched by the addition of 10 μL of 16% formic acid containing 800 nM of 5-carbon labeled 13C-2-HG). The protein was then precipitated by the addition of 2.5 volumes of acetonitrile followed by centrifugation (3000×g, minutes). The concentration of 2-HG in the resulting supernatants was measured by LC-MS (see below). LC-MS method. Reaction mixture supernatants were submitted to chromatographic separation on a BiobasicAX column (2.1 mm×20 mm, 5 μm particle, Thermo Scientific Inc.). The chromatographic mobile phases were A) 25 mM ammonium biocarbonate and B) acetonitrile (0.1% ammonium hydroxide). Nicotinamide was eluted at 1 ml/min using a 85-5% B gradient over 0.9 minutes (Agilent 1200SL LC system, Thermofisher LX-4 autosampler) and analyzed by multiple reaction monitoring (MRM) on a API4000 QTrap mass spectrometer (ABSciex, Framingham, Mass.) in the positive electrospray ionization (ESI+) mode. The mass transition for 2-HG and 13C-2-HG were 147→129 and 152→134, respectively.
Measurement: IC50 = 563 nM (pChEMBL 6.25)
Descriptors: MW 416.24, ALogP 3.2, HBA 7, HBD 2, PSA 100.47, QED 0.77
Compound (SMILES): CN[C@H]1CO[C@H]2[C@@H]1OC[C@@H]2Oc1cc2ncnc(Nc3ccc(Br)c(Cl)c3)c2cc1OC
InChIKey: BACURHXRJBKWQO-VRXWPRPYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: Inhibition of recombinant human N-terminal His6-tagged EphA2 (N598 to R890 residues) expressed in baculovirus using poly-EY as substrate after 180 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 521.8, ALogP 3.93, HBA 8, HBD 2, PSA 86.76, QED 0.5
Compound (SMILES): O=C(c1ccc(C2CC2)c(OCC2CC2)n1)N1CCC(O)(C(F)(F)F)C1
InChIKey: PKDOXNQAGIORSR-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: cAMP Assay: CHO cells expressing human CB1 or CB2 receptors are seeded 17-24 hours prior to the experiment 50.000 cells per well in a black 96 well plate with flat clear bottom (Corning Costar #3904) in DMEM (Invitrogen No. 31331), 1×HT supplement, with 10% fetal calf serum and incubated at 5% CO2 and 37 °C. in a humidified incubator. The growth medium was exchanged with Krebs Ringer Bicarbonate buffer with 1 mM IBMX and incubated at 30 °C. for 30 min. Compounds were added to a final assay volume of 100 μl and incubated for 30 min at 30 °C. Using the cAMP-Nano-TRF detection kit the assay (Roche Diagnostics) was stopped by the addition of 50 μl lysis reagent (Tris, NaCl, 1.5% Triton X100, 2.5% NP40, 10% NaN3) and 50 μl detection solutions (20 μM mAb Alexa700-cAMP 1:1, and 48 μM Ruthenium-2-AHA-cAMP) and shaken for 2 h at room temperature. The time-resolved energy transfer is measured by a TRF reader (Evotec Technologies GmbH), equipped with a ND:YAG laser as excitation source. The plate is measured twice with the excitation at 355 nm and at the emission with a delay of 100 ns and a gate of 100 ns, total exposure time 10 s at 730 (bandwidth 30 nm) or 645 nm (bandwidth 75 nm), respectively. The FRET signal is calculated as follows: FRET=T730-Alexa730-P(T645-B645) with P=Ru730-B730/Ru645-B645, where T730 is the test well measured at 730 nM, T645 is the test well measured at 645 nm, B730 and B645 are the buffer controls at 730 nm and 645 nm, respectively. cAMP content is determined from the function of a standard curve spanning from 10 μM to 0.13 nM cAMP.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 370.37, ALogP 2.89, HBA 4, HBD 1, PSA 62.66, QED 0.87
Compound (SMILES): CC(C)c1nc2c(c(Nc3ccc(C(F)(F)F)cc3)n1)CCN(c1ccccc1[N+](=O)[O-])CC2
InChIKey: SKWCNNVULAETLE-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Functional Assay: The assay was performed as described below, using HEK293 cells transfected with rat TRPV1 (rTRPV1/HEK293). These cells had a geneticin selection marker and were grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (50 units/mL), and 500 μg/mL geneticin in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 > 6700 nM (pChEMBL 5.173999786376953)
Descriptors: MW 471.48, ALogP 5.88, HBA 6, HBD 1, PSA 84.19, QED 0.37
Compound (SMILES): CCS(=O)(=O)NC(=O)C1=C(c2ccc(C)cc2)C[C@](c2ccc(OCCCCCC(F)(F)F)cc2)(C(F)(F)F)NC1=O
InChIKey: WEMZSVAXFIISGA-SANMLTNESA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: LCMS Assay: The MGAT enzyme reactions were performed in Corning FALCON® 96-well Polypropylene plates, in a total volume of 60 μL of 50 mM Potassium Phosphate buffer pH 7.4, containing a final concentration of 100 μM 2-oleoylglycerol, 15 μM oleoyl-Coenzyme A and 0.0013 μg/μL Human or Mouse MGAT-2 or 0.0026 μg/μL Rat recombinant MGAT-2 membranes expressed in Sf9 cells. Assay plates were run through a fully automated robotics system and shaken for 5 seconds every minute for a total 10 minutes. The reactions were then quenched with 120 μL of ice cold methanol containing 1 μg/mL 1,2-distearoyl-rac-glycerol as the internal standard. Plates were shaken for 2 minutes and spun down to remove protein precipitation. After the spin, samples were transferred to LC/MS compatible PCR plates. For LC/MS analysis, a ThermoFisher Surveyor pump, utilizing a Waters Symmetry C8, 50×2.1 mm column, was used for the chromatography of enzyme products. The buffer system consists of 0.1% formic acid in water with a mobile phase consisting 0.1% formic acid in methanol. The shallow gradient is 90-100% mobile phase in 0.2 min with a total run time of 2.3 min. The first 0.5 minutes of each injection was diverted to waste to eliminate the presence of Phosphate buffer in the enzymatic reaction. The column was run at 0.6 mL/min and a temperature of 65° C. Mass spectrometry analysis of the samples was performed on a ThermoFisher Quantum Triple quad utilizing APCI (+) as the mode of ionization.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 620.61, ALogP 5.69, HBA 5, HBD 2, PSA 101.57, QED 0.19
Compound (SMILES): CS(=O)(=O)NC1CCc2c(-c3ccc(C(F)(F)F)cc3)cncc21
InChIKey: OGZWZWDVHZEFCZ-UHFFFAOYSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Cellular Enzyme Assay: G-402 cells expressing CYP11 constructs were established as described above and maintained in McCoy's 5a Medium Modified, ATCC Catalog No. 30-2007 containing 10% FCS and 400 ug/ml G418 (Geneticin) at 37° C. under an atmosphere of 5% CO2/95% air. Cellular enzyme assays were performed in DMEM/F12 medium containing 2.5% charcoal treated FCS and appropriate concentration of substrate (0.3-10 uM 11-Deoxycorticosterone, 11-Deoxycortisol or Corticosterone). For assaying enzymatic activity, cells were plated onto 96 well plates and incubated for 16 h. An aliquot of the supernatant is then transferred and analyzed for the concentration of the expected product (Aldosterone for CYP11B2; Cortisol for CYP11B1). The concentrations of these steroids can be determined using HTRF assays from CisBio analyzing either Aldosterone or Cortisol.
Measurement: EC50 = 1961.9 nM (pChEMBL 5.710000038146973)
Descriptors: MW 356.37, ALogP 3.3, HBA 3, HBD 1, PSA 59.06, QED 0.92
Compound (SMILES): NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3)cc2)nn2c1NCCC2c1ccccc1N
InChIKey: ATVWSVZIBUCRNI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Kinase Assay: Compounds disclosed herein were tested for inhibition of Btk kinase activity in an assay based on time-resolved fluorescence resonance energy transfer methodology. Recombinant Btk was pre-incubated with the compounds disclosed herein at room temperature for 1 hour in an assay buffer containing 50 mM Tris pH7.4, 10 mM MgCl2, 2 mM MnCl2, 0.1 mM EDTA, 1 mM DTT, 20 nM SEB, 0.1% BSA, 0.005% tween-20. The reactions were initiated by the addition of ATP (at the concentration of ATP Km) and peptide substrate (Biotin-AVLESEEELYSSARQ-NH2). After incubating at room temperature for 1 h, an equal volume of stop solution containing 50 mM HEPES pH7.0, 800 mM KF, 20 mM EDTA, 0.1% BSA, Eu cryptate-conjugated p-Tyr66 antibody and streptavidin-labeled XL665 was added to stop the reaction. Plates were further incubated at room temperature for 1 hour, and then the TR-FRET signals (ex337 nm, em 620 nm/665 nm) were read on BMG PHERAstar FS instrument. The residual enzyme activity in presence of increasing concentrations of compounds was calculated based on the ratio of fluorescence at 615 nm to that at 665 nm.
Measurement: IC50 = 252 nM (pChEMBL 6.599999904632568)
Descriptors: MW 443.48, ALogP 4.57, HBA 6, HBD 3, PSA 108.19, QED 0.39