Hsp90 Inhibitors

Hsp90, short for heat shock protein 90, is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins, such as Her2/Erbb2, Akt, Raf1, Bcr-Abl, and mutated p53, in addition to other molecules involved in cell cycle regulation and immune responses.It supports for the appropriately folding of other proteins, offers help in protein degradation and also stabilizes some proteins needed for tumor growth. Hsp90 uses a host of cochaperones which not only regulate the ATPase activity and conformational dynamics but which also mediate interactions with Hsp90 client proteins.An hsp90 inhibitor usually binds to the ATP-binding pocket N-Terminal domain of hsp90, hence, blocks the binding of nucleotides to Hsp90.And some other inhibitors could bind at a second ATP-binding site in the C-terminal domain of Hsp90, thus disrupting the dimerization of the Hsp90 complex.