Definition

An orally bioavailable inhibitor of heat shock protein 90 (Hsp90), with potential antineoplastic activity. Upon oral administration, Hsp90 inhibitor NVP-BEP800 specifically binds to the NH(2)-terminal ATP-binding pocket of Hsp90 and specifically blocks Hsp90, which inhibits its chaperone function and promotes the proteasomal degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival, including ErbB2, B-Raf(V600E), Raf-1, and Akt. This prevents oncogenic pathway signaling mediated by these proteins and leads to the inhibition of tumor cell proliferation. Hsp90, a chaperone complex protein upregulated in a variety of tumor cell types, regulates the folding and degradation of many oncogenic signaling proteins.