Cobicistat (GS-9350): A Potent and Selective Inhibitor of Human CYP3A as a Novel Pharmacoenhancer

被引：157

作者：

Xu, Lianhong ^{[1
]}

Liu, Hongtao ^{[1
]}

Murray, Bernard P. ^{[2
]}

Callebaut, Christian ^{[3
]}

Lee, Melody S. ^{[2
]}

Hong, Allen ^{[1
]}

Strickley, Robert G. ^{[4
]}

Tsai, Luong K. ^{[3
]}

Stray, Kirsten M. ^{[3
]}

Wang, Yujin ^{[2
]}

Rhodes, Gerry R. ^{[2
]}

Desai, Manoj C. ^{[1
]}

机构：

[1] Gilead Sci Inc, Dept Med Chem, Foster City, CA 94404 USA

[2] Gilead Sci Inc, Drug Metab, Foster City, CA 94404 USA

[3] Gilead Sci Inc, Biol, Foster City, CA 94404 USA

[4] Gilead Sci Inc, Formulat, Foster City, CA 94404 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2010年 / 1卷 / 05期

关键词：

GS-9350; cobicistat; pharmacoenhancer; PK enhancer; CYP3A inhibitor; ritonavir; IMMUNODEFICIENCY-VIRUS PROTEASE; MECHANISM-BASED INACTIVATION; DRUG-DRUG INTERACTIONS; DOSE-RESPONSE; IN-VITRO; RITONAVIR; PHARMACOKINETICS; ELVITEGRAVIR; PREDICTION; INDUCTION;

D O I：

10.1021/ml1000257

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cobicistat (3, GS-9350) is a newly discovered, potent, and selective inhibitor of human cytochrome P450 3A (CYP3A) enzymes. In contrast to ritonavir, 3 is devoid of anti-HIV activity and is thus more suitable for use in boosting anti-HIV drugs without risking selection of potential drug-resistant HIV variants. Compound 3 shows reduced liability for drug interactions and may have potential improvements in tolerability over ritonavir. In addition, 3 has high aqueous solubility and can be readily coformulated with other agents.

引用

页码：209 / 213

页数：5

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