A Comparison of the In Vitro Inhibitory Effects of Thelephoric Acid and SKF-525A on Human Cytochrome P450 Activity
| العنوان: | A Comparison of the In Vitro Inhibitory Effects of Thelephoric Acid and SKF-525A on Human Cytochrome P450 Activity |
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| المؤلفون: | HyunHee Do, Kyung-Sik Song, Oh Kwang Kwon, Eun-Ju Yang, Min-Gyu Song, Sangkyu Lee, Jong-Sup Bae, Tae Cheon Jeong |
| المصدر: | Biomolecules & Therapeutics |
| بيانات النشر: | The Korean Society of Applied Pharmacology, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Cytochrome P450, Pharmacology, digestive system, Biochemistry, chemistry.chemical_compound, Non-competitive inhibition, Drug Discovery, heterocyclic compounds, Thelephoric acid, CYP2C8, CYP2C9, biology, CYP3A4, CYP1A2, CYP2E1, Non-specific inhibitor, Polyozellin, chemistry, biology.protein, Molecular Medicine, Original Article, SKF-525A |
| الوصف: | Thelephoric acid is an antioxidant produced by the hydrolysis of polyozellin, which is isolated from Polyozellus multiplex. In the present study, the inhibitory effects of polyozellin and thelephoric acid on 9 cytochrome P450 (CYP) family members (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) were examined in pooled human liver microsomes (HLMs) using a cocktail probe assay. Polyozellin exhibited weak inhibitory effects on the activities of all 9 CYPs examined, whereas thelephoric acid exhibited dose- and time-dependent inhibition of all 9 CYP isoforms (IC50 values, 3.2-33.7 μM). Dixon plots of CYP inhibition indicated that thelephoric acid was a competitive inhibitor of CYP1A2 and CYP3A4. In contrast, thelephoric acid was a noncompetitive inhibitor of CYP2D6. Our findings indicate that thelephoric acid may be a novel, non-specific CYP inhibitor, suggesting that it could replace SKF-525A in inhibitory studies designed to investigate the effects of CYP enzymes on the metabolism of given compounds. |
| تدمد: | 1976-9148 2005-4483 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::434e43495d411cc2f12cb6a5eae11aaa https://doi.org/10.4062/biomolther.2013.107 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....434e43495d411cc2f12cb6a5eae11aaa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19769148 20054483 |
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