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变构 Hsp90 ATP 酶激动剂的设计作为新型抗癌先导物。

Design of Allosteric Stimulators of the Hsp90 ATPase as New Anticancer Leads.

机构信息

Istituto di Chimica del Riconoscimento Molecolare, CNR, via Mario Bianco, 9, 20131, Milan, Italy.

Dipartimento di Chimica, Università degli Studi di Milano, via Golgi, 19, 20133, Milan, Italy.

出版信息

Chemistry. 2017 Apr 19;23(22):5188-5192. doi: 10.1002/chem.201700169. Epub 2017 Mar 22.

DOI:10.1002/chem.201700169
PMID:28207175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5927549/
Abstract

Allosteric compounds that stimulate Hsp90 adenosine triphosphatase (ATPase) activity were rationally designed, showing anticancer potencies in the low micromolar to nanomolar range. In parallel, the mode of action of these compounds was clarified and a quantitative model that links the dynamic ligand-protein cross-talk to observed cellular and in vitro activities was developed. The results support the potential of using dynamics-based approaches to develop original mechanism-based cancer therapeutics.

摘要

别构化合物可刺激热休克蛋白 90（Hsp90）三磷酸腺苷（ATP）酶的活性，其抗癌活性在低微摩尔至纳摩尔范围内。与此同时，这些化合物的作用模式也得到了阐明，并建立了一个定量模型，将动态配体-蛋白相互作用与观察到的细胞和体外活性联系起来。这些结果支持了利用基于动力学的方法开发原创机制的癌症治疗药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183a/5927549/155639ad6a05/nihms959435f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183a/5927549/d64891587042/nihms959435f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183a/5927549/155639ad6a05/nihms959435f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183a/5927549/d64891587042/nihms959435f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183a/5927549/155639ad6a05/nihms959435f2.jpg

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