ADMET In Vitro Profiling: Utility and Applications in Lead Discovery

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI:10.1002/0471266949.BMC118

E. Kerns, L. Di, G. Carter

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引用次数: 1

Abstract

ADMET properties are a vital integral part of drug discovery because they determine the pharmacokinetics and safety of clinical development candidates. Diverse ADMET profiling assays have been developed and implemented to provide property data for drug discovery team decision making. Their utility and applications in lead discovery include the following: lead selection, diagnosis of poor PK, guidance for structure modification, solving specific project team property issues, providing accurate biological data for SAR, selecting compounds for in vivo PK and PD studies, and improving dosing for optimum exposure in vivo. ADMET properties are discussed along with case studies and assays. Keywords: absorption; ADMET; assays; blood–brain barrier; bioassay; Caco-2; cytochrome P450 (CYP); distribution; drug–drug interaction; drug-like properties; excretion; hERG blocking; in vitro assay; lipophilicity; metabolism; optimization; PAMPA; permeability; pharmacokinetics; physicochemical; pKa; protein binding; rule of five; stability; solubility; toxicity; transporters

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ADMET体外分析:在铅发现中的效用和应用

ADMET特性是药物发现的重要组成部分，因为它们决定了临床开发候选药物的药代动力学和安全性。不同的ADMET分析分析已经被开发和实施，为药物发现团队的决策提供属性数据。它们在先导物发现中的用途和应用包括:先导物的选择、不良PK的诊断、结构修饰的指导、解决特定项目团队属性问题、为SAR提供准确的生物学数据、为体内PK和PD研究选择化合物、改善剂量以获得最佳体内暴露。ADMET的性质与案例研究和分析一起讨论。关键词:吸收;ADMET;化验;血脑屏障;生物测定;Caco-2;细胞色素P450 (CYP);分布;药物之间的相互作用;药物类属性;排泄;hERG阻塞;体外测定;亲油性;新陈代谢;优化;南美大草原;渗透率;药物动力学;物理化学;pKa;蛋白质绑定;五法则;稳定;溶解度;毒性;转运蛋白

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Burger's Medicinal Chemistry and Drug Discovery

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