Discovery of hybrid Hsp90 inhibitors and their anti-neoplastic effects against gefitinib-resistant non-small cell lung cancer (NSCLC)

被引：23

作者：

Jeong, Chul-Ho ^{[1
,2
]}

Park, Hee Baek ^{[2
]}

Jang, Won Jun ^{[1
]}

Jung, Su Hyun ^{[2
]}

Seo, Young Ho ^{[1
,2
]}

机构：

[1] Keimyung Univ, Coll Pharm, Taegu 704701, South Korea

[2] Keimyung Univ, Inst New Drug Dev, Taegu 704701, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 01期

关键词：

Hsp90; Lung cancer; Gefitinib resistance; Inhibitor; Rational design; EGFR MUTATIONS; CHAPERONE; HALLMARKS; PROTEINS;

D O I：

10.1016/j.bmcl.2013.11.034

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Heat shock protein 90 (Hsp90) represents an attractive cancer therapeutic target due to its role in the stabilization and maturation of many oncogenic proteins. We have designed a series of hybrid Hsp90 inhibitors by connecting the resorcinol ring of VER-49009 (2) and the trimethoxyphenyl ring of PU3 (3) using structure-based approach. Subsequent testing established that compound 1f inhibited gefitinib-resistant H1975 cell proliferation, brought about the degradation of Hsp90 client proteins including EGFR, Met, Her2 and Akt and induced the expression of Hsp70. The design, synthesis, and evaluation of 1f are described herein. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：224 / 227

页数：4

共 19 条

[1] Trends in Utilization of the Pharmacological Potential of Chalcones [J].