Small-Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1a

被引：222

作者：

Buckley, Dennis L. ^{[1
,2
,3
,4
]}

Gustafson, Jeffrey L. ^{[1
,2
,3
,4
]}

Van Molle, Inge ^{[5
]}

Roth, Anke G. ^{[1
,2
,3
,4
]}

Tae, Hyun Seop ^{[1
,2
,3
,4
]}

Gareiss, Peter C. ^{[1
,2
,3
,4
]}

Jorgensen, William L. ^{[1
,2
,3
,4
]}

Ciulli, Alessio ^{[5
]}

Crews, Craig M. ^{[1
,2
,3
,4
]}

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06511 USA

[2] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA

[3] Yale Univ, Dept Pharmacol, New Haven, CT 06511 USA

[4] Yale Univ, Ctr Mol Discovery, New Haven, CT 06511 USA

[5] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2012年 / 51卷 / 46期

基金：

英国生物技术与生命科学研究理事会;

关键词：

drug design; E3 ubiquitin ligases; protein crystallography; protein-protein interactions; structure-based design; PROTEIN-PROTEIN INTERACTIONS; STAPLED P53 PEPTIDE; UBIQUITIN LIGASE; DRUG TARGETS; DISCOVERY; RECOGNITION; ANTAGONISTS; ACTIVATION; INTERFACES; PATHWAY;

D O I：

10.1002/anie.201206231

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

By design: Novel small-molecule inhibitors of the interaction between the von Hippel-Lindau ligase (VHL) and its molecular target HIF1α, a transcription factor involved in oxygen sensing, have been developed and studied. The most potent inhibitor binds with an IC50 value of 0.9-μM and is thus the first sub-micromolar inhibitor of the VHL-HIF1α interaction. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

收藏

页码：11463 / 11467

页数：5

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