R115866抑制all-trans-retinoic酸代谢和施加retinoidal效果在啮齿动物。
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Stoppie P,风满楼M, Borghgraef P, Dillen L,古森斯J, Sanz G, Szel H,范霍夫C, Van Nyen G, G诺贝尔奖,Vanden Bossche H, Venet M, willemsen G, Van Wauwe J
R115866抑制all-trans-retinoic酸代谢和施加retinoidal效果在啮齿动物。
J Exp其他杂志》2000年4月,293(1):304 - 12所示。
- PubMed ID
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10734183 (在PubMed]
- 文摘
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All-trans-retinoic酸(RA)调节上皮分化和生长核RA通过激活特定的受体(rar)。因为高速新陈代谢很大程度上削弱了类风湿性关节炎的生物功效,我们寻求化合物能够抑制代谢类维生素a的崩溃。本研究确定R115866新型抑制剂的细胞色素P450 (CYP)介导的RA代谢。在体外,摩尔浓度R115866 CYP26抑制RA的转换,RA-inducible RA代谢酶。体内,口服R115866(2.5毫克/公斤)大鼠诱导标志和瞬态血浆中内源性RA水平的增加,皮肤、脂肪、肾脏和睾丸。符合其能力增强内生RA内容组织,发现R115866施加retinoidal活动。像RA,标题化合物:1)抑制阴道estrogen-stimulated鼠角质化;2)诱导小鼠耳部皮肤表皮增生;3)改变了老鼠的尾巴表皮从帕拉- orthokeratotic皮肤类型;4)在大鼠肝脏差异CYP26 mRNA的表达。 Furthermore, we found that the keratinization-suppressive and CYP26-inducing activities of R115866 could be reversed by concomitant administration of the RAR antagonist, AGN193109. Our data characterize R115866 as a potent, orally active inhibitor of RA metabolism, capable of enhancing RA levels and displaying retinoidal actions. These activities are reversed by RAR antagonism, supporting the idea that the actions of R115866 result from increased availability of endogenous RA and improved RAR triggering.
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