Blocking the chaperone kinome pathway: Mechanistic insights into a novel dual inhibition approach for supra-additive suppression of malignant tumors

► Withaferin A and 17-DMAG synergistically inhibit the Hsp90-Cdc37 chaperone pair. ► Binding of WA to Cdc37 cleft suppresses its kinase binding activity. ► 17-DMAG binding to the association complex results in H-bonds with 60% clustering. ► The ligands' bound complex was found structurally and thermodynamically stable.