Design of allosteric stimulators of the HSP90 ATPase as novel anticancer leads

Alloster ic compounds that stimu late Hsp90 ade- nosine triphosph atase(ATPase) activity were ration ally de- signed, showing anticancer potenc ies in the low micromo- lar to nanomo lar range. In parallel, the mode of action of these comp ounds was clarified andaquantitative model that links the dynam ic ligand -protein cross-tal ktoob- served cellular andinvitro activities was develo ped. The results suppo rt the potentia lofusing dynamics- based ap- proaches to develo porigina lmechanis m-based cancer therapeutics