Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity.
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.


RESULTS
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
Hence, tamoxifen and its metabolite are the first members of a new pharmacological class of Hsp90 activators.
Zhao
Rongmin
R
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
Leung
Elisa
E
Grüner
Stefan
S
Schapira
Matthieu
M
Houry
Walid A
WA
D000251:Adenosine Triphosphatases / Q000187:drug effects* / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D018841:HSP90 Heat-Shock Proteins / Q000819:agonists*; D006801:Humans; D018832:Molecular Chaperones / Q000187:drug effects; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D013629:Tamoxifen; C016601:afimoxifene; D000251:Adenosine Triphosphatases