Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase
Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase
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DOI：
10.1016/s0968-0896(02)00253-5
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发表时间：
2002-11-01
影响因子：
3.5
通讯作者：
Rosen, N
中科院分区：
文献类型：
--
作者：
Chiosis, G;Lucas, B;Rosen, N
首次报道了一种嘌呤-支架热休克蛋白90抑制剂文库的合成和表征。嘌呤支架代表了一个平台，用于创建易于合成和衍生化的可口服给药的可溶性分子。该系列中最活跃的化合物(71)与HSP90的结合能力与天然产品衍生物17AAG相当，后者目前正处于癌症治疗的I期临床试验中。71诱导Her2酪氨酸激酶的降解，并在低微摩尔浓度(IC50=2um)下阻止MCF-7乳腺癌细胞株的生长。(C)2002爱思唯尔科学有限公司。保留所有权利。
The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71) exhibits binding to hsp90 comparable to the natural product derivative 17AAG that is now in Phase I clinical trial as a cancer therapeutic. 71 Induces the degradation of Her2 tyrosine kinase and arrests the MCF-7 breast cancer cell line at low micromolar concentrations (IC50 = 2 muM). (C) 2002 Elsevier Science Ltd. All rights reserved.