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

Ilda D'Annessa; Sara Sattin; Jiahui Tao; Marzia Pennati; Carlos Sànchez-Martìn; Elisabetta Moroni; Andrea Rasola; Nadia Zaffaroni; David A. Agard; Anna Bernardi; Giorgio Colombo

doi:10.1002/chem.201700169

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

Ilda D'Annessa, Sara Sattin, Jiahui Tao, Marzia Pennati, Carlos Sànchez-Martìn, Elisabetta Moroni, Andrea Rasola, Nadia Zaffaroni, David A. Agard, Anna Bernardi, Giorgio Colombo

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	5188-5192
Number of pages	5
Journal	Chemistry - A European Journal
Volume	23
Issue number	22
DOIs	https://doi.org/10.1002/chem.201700169
Publication status	Published - Jan 1 2017

Keywords

allostery
drug design
hsp90
modulators
molecular dynamics

ASJC Scopus subject areas

Chemistry(all)

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10.1002/chem.201700169

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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.",

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AU - D'Annessa, Ilda

AU - Sattin, Sara

AU - Tao, Jiahui

AU - Pennati, Marzia

AU - Sànchez-Martìn, Carlos

AU - Moroni, Elisabetta

AU - Rasola, Andrea

AU - Zaffaroni, Nadia

AU - Agard, David A.

AU - Bernardi, Anna

AU - Colombo, Giorgio

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KW - molecular dynamics

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

Abstract

Keywords

ASJC Scopus subject areas

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