Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity.

ABSTRACT:

Background

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.

SUBMITTER: Zhao R 

PROVIDER: S-EPMC2848575 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature