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二羟基苯基酰胺作为热休克蛋白90分子伴侣的抑制剂

Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone.

作者信息

Kung Pei-Pei, Funk Lee, Meng Jerry, Collins Michael, Zhou Joe Zhongxiang, Johnson M Catherine, Ekker Anne, Wang Jeff, Mehta Pramod, Yin Min-Jean, Rodgers Caroline, Davies Jay F, Bayman Eileen, Smeal Tod, Maegley Karen A, Gehring Michael R

机构信息

Pfizer Global Research and Development, La Jolla Laboratories, 10770, Science Center Dr., San Diego, CA 92121, USA.

出版信息

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6273-8. doi: 10.1016/j.bmcl.2008.09.081. Epub 2008 Sep 26.

DOI:10.1016/j.bmcl.2008.09.081
PMID:18929486
Abstract

Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a Hsp90 competitive binding assay. A class of novel and potent small molecule Hsp90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human cancer cell lines in vitro, with IC(50) values averaging 20 nM.

摘要

在Hsp90竞争性结合试验中，利用X射线晶体结构信息优化了一个高通量筛选命中化合物的活性。由此鉴定出一类新型强效小分子Hsp90抑制剂。对映体纯的化合物31和33在基于PGA的竞争性结合试验中表现出活性，并在体外抑制多种人类癌细胞系的增殖，IC(50)值平均为20 nM。

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