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ChEMBL ligand: CHEMBL178090 |
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DB | Assay description | Assay Type | Standard value | Standard parameter | Original value | Original units | Original parameter | Reference |
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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 | 7.4 | pKi | 40 | nM | Ki | US-8609708-B2. Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer (2013) |
GtoPdb | - | - | 7.4 | pKi | 40 | 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 | 4.77 | pIC50 | 16900 | 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 | 6.57 | pIC50 | 268 | 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 | 6.57 | pIC50 | 268 | nM | IC50 | US-8609708-B2. Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer (2013) |
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 | 6.7 | pIC50 | 200 | 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 | 4.33 | pIC50 | 47170 | 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 34:
Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
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]