Neuro-Medicine Center, Korea Institute of Science and Technology, Seoul, Republic of Korea.
Bioorg Med Chem Lett. 2011 Mar 15;21(6):1593-7. doi: 10.1016/j.bmcl.2011.01.117. Epub 2011 Feb 2.
Novel 2,4-diaminoquinazoline derivatives originating from a virtual screening approach were designed, synthesized and their biological activities as heat shock protein 90 (Hsp90) inhibitors were evaluated. The prepared compounds exhibited significant anti-proliferative activities against DU-145, HT-29, HCT-116, A375P and MCF-7 cancer cell lines. The selected compounds were tested against Her2, a client protein of Hsp90, and showed significant reduction in Her2 protein expression. Compound 6b was found the most potent, reduced Her2 protein expression levels and induced Hsp70 protein expression levels significantly.
新型 2,4-二氨基喹唑啉衍生物源于虚拟筛选方法，被设计、合成，并评估了它们作为热休克蛋白 90（Hsp90）抑制剂的生物活性。所制备的化合物对 DU-145、HT-29、HCT-116、A375P 和 MCF-7 癌细胞系表现出显著的抗增殖活性。选择的化合物被测试针对 Her2，Hsp90 的一个客户蛋白，并且显示出对 Her2 蛋白表达的显著减少。化合物 6b 被发现是最有效的，降低了 Her2 蛋白表达水平，并显著诱导了 Hsp70 蛋白表达水平。
