A Comparison of the In Vitro Inhibitory Effects of Thelephoric Acid and SKF-525A on Human Cytochrome P450 Activity

Song, Min; Do, HyunHee; Kwon, Oh Kwang; Yang, Eun-Ju; Bae, Jong-Sup; Jeong, Tae Cheon; Song, Kyung-Sik; Lee, Sangkyu

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자료유형: 학술저널

저자정보: Song, Min (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Do, HyunHee (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Kwon, Oh Kwang (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Yang, Eun-Ju (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Bae, Jong-Sup (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Jeong, Tae Cheon (College of Pharmacy, Yeungnam University) Song, Kyung-Sik (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Lee, Sangkyu (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)

저널정보: 한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제22권 제2호

발행연도: 2014.1

수록면: 155 - 160 (6page)

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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 ($IC_{50}$ values, $3.2-33.7{\mu}M$). 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.

#Thelephoric acid #Polyozellin #SKF-525A #Cytochrome P450 #Non-specific inhibitor

참고문헌 (21)

참고문헌 신청

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