Structure-activity relationship of isoform selective inhibitors of Rac1/1b GTPase nucleotide binding

被引：17

作者：

Beausoleil, Eric ^{[1
]}

Chauvignac, Cedric ^{[1
]}

Taverne, Thierry ^{[1
]}

Lacombe, Sandrine ^{[1
]}

Pognante, Laure ^{[1
]}

Leblond, Bertrand ^{[1
]}

Pallares, Diego ^{[1
]}

De Oliveira, Catherine ^{[1
]}

Bachelot, Florence ^{[1
]}

Carton, Rachel ^{[1
]}

Peillon, Helene ^{[1
]}

Coutadeur, Severine ^{[1
]}

Picard, Virginie ^{[1
]}

Lambeng, Nathalie ^{[1
]}

Desire, Laurent ^{[1
]}

Schweighoffer, Fabien ^{[1
]}

机构：

[1] Exonhit Therapeut, F-75013 Paris, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 19期

关键词：

Rac; Alkaloid; GTP binding protein; Rho GTPase; Molecular docking; SMALL-MOLECULE INHIBITOR; SPLICE VARIANT; RHO-GTPASES; CANCER-CELLS; IN-VIVO; FAMILY; DISEASE; CHELERYTHRINE; SANGUINARINE; EXPRESSION;

D O I：

10.1016/j.bmcl.2009.08.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis of a series of berberine, phenantridine and isoquinoline derivatives was realized to explore their Rho GTPase nucleotide inhibitory activity. The compounds were evaluated in a nucleotide binding competition assay against Rac1, Rac1b, Cdc42 and in a cellular Rac GTPase activation assay. The insertion of 19 AA in the splice variant Rac1b is shown to be sufficient to introduce a conformational difference that allows compounds 4, 21, 22, and 26 to exhibit selective inhibition of Rac 1b over Rac1. (C) 2009 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5594 / 5598

页数：5

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