Potent Farnesyltransferase Inhibitors with 1,4-Diazepane Scaffolds as Novel Destabilizing Microtubule Agents in Hormone-Resistant Prostate Cancer

被引：18

作者：

Wlodarczyk, Nicolas ^{[1
]}

Le Broc-Ryckewaert, Delphine ^{[2
]}

Gilleron, Pauline ^{[1
]}

Lemoine, Amelie ^{[1
]}

Farce, Amaury ^{[1
]}

Chavatte, Philippe ^{[1
]}

Dubois, Joelle ^{[3
]}

Pommery, Nicole ^{[2
]}

Henichart, Jean-Pierre ^{[1
]}

Furman, Christophe ^{[2
]}

Millet, Regis ^{[1
]}

机构：

[1] Univ Lille Nord France, Inst Chim Pharmaceut, EA4481, IFR114, F-59006 Lille, France

[2] Univ Lille Nord France, Fac Sci Pharmaceut & Biol Lille, EA4483, IFR114, F-59006 Lille, France

[3] CNRS, Ctr Rech Gif, Inst Chim Subst Nat, UPR2301, F-91198 Gif Sur Yvette, France

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 05期

关键词：

FARNESYL TRANSFERASE; PROTEIN FARNESYLTRANSFERASE; PEPTIDOMIMETIC INHIBITOR; CRYSTALLOGRAPHIC ANALYSIS; BIOLOGICAL-ACTIVITY; ANTITUMOR-ACTIVITY; IN-VITRO; CENP-F; GROWTH; PACLITAXEL;

D O I：

10.1021/jm101067y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of potent farnesyltransferase inhibitors based on a 1,4-diazepane scaffold was synthesized with protein farnesyltransferase inhibition potencies in the low nanomolar range. The compounds block the growth on two hormone-resistant tumor prostatic cell lines (DU145 and PC3). The advanced cellular evaluation of the more potent farnesyltransferase inhibitors was explored and revealed a disorganization of tubulin in PC3 cells.

引用

页码：1178 / 1190

页数：13

共 4 条

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