The protein farnesyltransferase inhibitor tipifarnib as a new lead for the development of drugs against Chagas disease

被引：72

作者：

Hucke, O

Gelb, MH

Verlinde, CLMJ

Buckner, FS ^{[1
]}

机构：

[1] Univ Washington, Dept Med, Seattle, WA 98195 USA

[2] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA

[3] Univ Washington, Dept Chem, Seattle, WA 98195 USA

[4] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[5] Univ Washington, Biomol Struct Ctr, Seattle, WA 98195 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 17期

关键词：

D O I：

10.1021/jm050441z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tipifarnib (R115777), an inhibitor of human protein farnesyltransferase (PFT), is shown to be a highly potent inhibitor of Trypanosoma cruzi growth (ED50 = 4 nM). Surprisingly, this is due to the inhibition of cytochrome P450 sterol 14-demethylase (CYP51, EC 1.14.13.70). Homology models of the T cruzi CYP51 were used for the prediction of the binding modes of the substrate lanosterol and of Tipifarnib, providing a basis for the design of derivatives with selectivity for TcCYP51 over human PFT.

引用

页码：5415 / 5418

页数：4

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