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

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.

SUBMITTER: D'Annessa I

PROVIDER: S-EPMC5927549 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

D'Annessa Ilda I Sattin Sara S Tao Jiahui J Pennati Marzia M Sànchez-Martìn Carlos C Moroni Elisabetta E Rasola Andrea A Zaffaroni Nadia N Agard David A DA Bernardi Anna A Colombo Giorgio G

Chemistry (Weinheim an der Bergstrasse, Germany) 20170322 22

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 therape ...[more]

PMID: 28207175

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