Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity

Hsp90 is an essential molecular chaperone that is also a novel anti-cancer drug target. There is growing interest in developing new drugs that modulate Hsp90 activity. Methodology/principal findings: Using a virtual screening approach, 4-hydroxytamoxifen, the active metabolite of the anti-estrogen drug tamoxifen, was identified as a putative Hsp90 ligand. Surprisingly, while all drugs targeting Hsp90 inhibit the chaperone ATPase activity, it was found experimentally that 4-hydroxytamoxifen and tamoxifen enhance rather than inhibit Hsp90 ATPase. Conclusions/significance: Hence, tamoxifen and its metabolite are the first members of a new pharmacological class of Hsp90 activators.

Hence, tamoxifen and its metabolite are the first members of a new pharmacological class of Hsp90 activators.