Compositions and Methods for Inhibiting HSP90/HSP70 Machinery

摘要

Pharmaceutical compositions including an effective amount of a capsaicin and inhibitors of Hsp90 to decrease or inhibit Hsp70 and Hsp90 chaperone pathways in cells are disclosed. Methods of inhibiting the Hsp70 and Hsp90 chaperone pathways including contacting cells expressing the Hsp70/Hsp90 complex with an effective amount of a capsaicin in combination with inhibitors of Hsp90 to decrease or inhibit the Hsp70 and Hsp90 chaperone pathways are provided. The methods can reduce the viability of target cells, for example, by increasing apoptosis or pro-apoptotic pathways. In preferred embodiments, the methods reduce or do not increase Hsp70, Hsp90, Hsp40, or HOP expression; reduce or do not increase heat shock response; reduce or do not increase pro-survival pathways in cells. Methods of treating cancer and other diseases using the disclosed compositions and methods are provided.

主权项

1. A pharmaceutical composition comprising an effective amount of
a) a capsaicin, a synthetic capsaicin, or a derivative, analog or prodrug, or a pharmacologically active salt thereof to reduce, decrease, or inhibit the Hsp70; and b) one or more inhibitors of Hsp90to reduce, decrease, or inhibit the Hsp90 compared to a control.