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

Authors :: D'Annessa I
Sattin S
Tao J
Pennati M
Sànchez-Martìn C
Moroni E
Rasola A
Zaffaroni N
Agard DA
Bernardi A
Colombo G
Source :: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2017 Apr 19; Vol. 23 (22), pp. 5188-5192. Date of Electronic Publication: 2017 Mar 22.
Publication Year :: 2017
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.<br /> (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)