ChEMBL ligand: CHEMBL359657
CYP2A6/Cytochrome P450 2A6 in Human [ChEMBL: CHEMBL5282] [GtoPdb: 1321] [UniProtKB: P11509] There should be some charts here, you may need to enable JavaScript!
CYP2B6/Cytochrome P450 2B6 in Human [ChEMBL: CHEMBL4729] [GtoPdb: 1324] [UniProtKB: P20813] There should be some charts here, you may need to enable JavaScript!
CYP3A4/Cytochrome P450 3A4 in Human [ChEMBL: CHEMBL340] [GtoPdb: 1337] [UniProtKB: P08684] There should be some charts here, you may need to enable JavaScript!

DB	Assay description	Assay Type	Standard value	Standard parameter	Original value	Original units	Original parameter	Reference
CYP2A6/Cytochrome P450 2A6 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5282] [GtoPdb: 1321] [UniProtKB: P11509]
ChEMBL	Inhibition of human CYP2A6 expressed in insect cell membranes assessed as reduction in enzyme-mediated coumarin 7-hydroxylation in presence of glucose-6-phosphate, glucose-6-phosphate dehydrogenase and NADPH-generating system by fluorometry	B	7.7	pKi	20	nM	Ki	US-8609708-B2. Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer (null)
GtoPdb	-	-	7.7	pKi	20	nM	Ki	J Med Chem (2005) 48: 224-39 [PMID:15634016]
ChEMBL	Inhibition Assay: The inhibition of human CYP2A6-mediated 7-hydroxy coumarin formation was evaluated in the presence of 95 selected test compounds in a standard assay (Greenlee et al., J Pharmacol Exp Ther, 1978). Our first studies were with highly purified human CYP2A6 that provided a convenient and relatively high-throughput measure of CYP2A6 inhibition.	B	5.13	pIC50	7440	nM	IC50	US-8609708-B2. Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer (2013)
ChEMBL	Inhibition Assay: The inhibition of human CYP2A6-mediated 7-hydroxy coumarin formation was evaluated in the presence of 95 selected test compounds in a standard assay (Greenlee et al., J Pharmacol Exp Ther, 1978). Our first studies were with highly purified human CYP2A6 that provided a convenient and relatively high-throughput measure of CYP2A6 inhibition.	B	6.76	pIC50	172	nM	IC50	US-8609708-B2. Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer (2013)
ChEMBL	Inhibition of human CYP2A6 expressed in insect cell microsomes assessed as reduction in enzyme-mediated coumarin 7-hydroxylation	B	6.77	pIC50	170	nM	IC50	US-8609708-B2. Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer (null)
ChEMBL	Inhibition Assay: To gain insight into the selectivity of the synthetic compounds for inhibition of other CYPs, we examined the major CYPs present in human liver. Prior to these studies we showed that the nicotine analogs were quite metabolically stable in the presence of mouse or rat or human liver microsomes (i.e., T1/2>60 mins). That the nicotine analogs showed low or no inhibitory activity against other CYPs suggests that the inhibitors examined selectively inhibited CYP2A6. A typical incubation mixture (final volume 0.25 mL) contained 50 mM Tris or KPhos buffer (pH 7.5), 0.5 mM NADP+, 2.0 mM G6P, 1 U of G6P dehydrogenase and 0.6 mg DETAPAC and the inhibitor was added last to minimize interaction with the protein. After mixing on ice, the reaction was initiated by the addition of substrate and incubated at 37° C. with shaking in air. Organic extracts were analyzed by fluorescence (for fluorometric substrates) or injected onto a Hitachi L-7100 system equipped with a Hitachi L-7400 UV detector.	B	6.8	pIC50	160	nM	IC50	US-8906943-B2. Synthetic compounds and methods to decrease nicotine self-administration (2014)
CYP2B6/Cytochrome P450 2B6 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4729] [GtoPdb: 1324] [UniProtKB: P20813]
ChEMBL	Inhibition Assay: To gain insight into the selectivity of the synthetic compounds for inhibition of other CYPs, we examined the major CYPs present in human liver. Prior to these studies we showed that the nicotine analogs were quite metabolically stable in the presence of mouse or rat or human liver microsomes (i.e., T1/2>60 mins). That the nicotine analogs showed low or no inhibitory activity against other CYPs suggests that the inhibitors examined selectively inhibited CYP2A6. A typical incubation mixture (final volume 0.25 mL) contained 50 mM Tris or KPhos buffer (pH 7.5), 0.5 mM NADP+, 2.0 mM G6P, 1 U of G6P dehydrogenase and 0.6 mg DETAPAC and the inhibitor was added last to minimize interaction with the protein. After mixing on ice, the reaction was initiated by the addition of substrate and incubated at 37° C. with shaking in air. Organic extracts were analyzed by fluorescence (for fluorometric substrates) or injected onto a Hitachi L-7100 system equipped with a Hitachi L-7400 UV detector.	B	4.28	pIC50	52200	nM	IC50	US-8906943-B2. Synthetic compounds and methods to decrease nicotine self-administration (2014)
CYP3A4/Cytochrome P450 3A4 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL340] [GtoPdb: 1337] [UniProtKB: P08684]
ChEMBL	Inhibition Assay (Testosterone Hydroxylase): To gain insight into the selectivity of the synthetic compounds, nicotine, nicotine related alkaloids and nicotine metabolites for inhibition of other CYPs, we examined the major CYP present in human liver (i.e., CYP 3A4). That the CYP2A6 inhibitors showed low or no inhibitory activity against CYP3A4 suggests that the inhibitors examined selectively inhibited CYP2A6.	B	4.23	pIC50	58720	nM	IC50	US-8609708-B2. Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer (2013)
ChEMBL	Inhibition Assay (Testosterone Hydroxylase): To gain insight into the selectivity of the synthetic compounds, nicotine, nicotine related alkaloids and nicotine metabolites for inhibition of other CYPs, we examined the major CYP present in human liver (i.e., CYP 3A4). That the CYP2A6 inhibitors showed low or no inhibitory activity against CYP3A4 suggests that the inhibitors examined selectively inhibited CYP2A6.	B	4.24	pIC50	56990	nM	IC50	US-8609708-B2. Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer (2013)
ChEMBL	Inhibition Assay (Testosterone Hydroxylase): To gain insight into the selectivity of the synthetic compounds, nicotine, nicotine related alkaloids and nicotine metabolites for inhibition of other CYPs, we examined the major CYP present in human liver (i.e., CYP 3A4). That the CYP2A6 inhibitors showed low or no inhibitory activity against CYP3A4 suggests that the inhibitors examined selectively inhibited CYP2A6.	B	4.81	pIC50	15330	nM	IC50	US-8609708-B2. Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer (2013)

ChEMBL data shown on this page come from version 33:

Mendez D, Gaulton A, Bento AP, Chambers J, De Veij M, Félix E, Magariños MP, Mosquera JF, Mutowo P, Nowotka M, Gordillo-Marañón M, Hunter F, Junco L, Mugumbate G, Rodriguez-Lopez M, Atkinson F, Bosc N, Radoux CJ, Segura-Cabrera A, Hersey A, Leach AR. (2019) 'ChEMBL: towards direct deposition of bioassay data' Nucleic Acids Res., 47(D1). DOI: 10.1093/nar/gky1075. [EPMCID:30398643]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]