细胞色素 P450 激活前药。
Cytochrome P450-activated prodrugs.
机构信息
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94158-2517, USA.
出版信息
Future Med Chem. 2013 Feb;5(2):213-28. doi: 10.4155/fmc.12.197.
Abstract
A prodrug is a compound that has negligible, or lower, activity against a specified pharmacological target than one of its major metabolites. Prodrugs can be used to improve drug delivery or pharmacokinetics, to decrease toxicity, or to target the drug to specific cells or tissues. Ester and phosphate hydrolysis are widely used in prodrug design because of their simplicity, but such approaches are relatively ineffective for targeting drugs to specific sites. The activation of prodrugs by the cytochrome P450 system provides a highly versatile approach to prodrug design that is particularly adaptable for targeting drug activation to the liver, to tumors or to hypoxic tissues.
摘要
前药是一种化合物，其对特定药理靶点的活性（比其主要代谢物）可忽略不计或较低。前药可用于改善药物递送或药代动力学，降低毒性，或使药物靶向特定细胞或组织。酯和磷酸酯水解广泛用于前药设计，因为它们简单，但这些方法对于将药物靶向特定部位相对无效。细胞色素 P450 系统对前药的激活提供了一种非常灵活的前药设计方法，特别适合将药物激活靶向肝脏、肿瘤或缺氧组织。
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2
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