Onalespib

Onalespib, also known as AT13387, is a selective inhibitor of Hsp90 (IC50 = 18 nM). It induces the degradation of specific Hsp90 client proteins, including mutant EGFR, for up to seven days in tumor cell lines in vitro and up to three days in vivo. Onalespib is retained in tumor xenografts and is efficacious in a range of xenograft models. It differs from other HSP90 inhibitors in its longer duration of target inhibition and its favorable toxicity profile in phase I studies in patients with refractory solid tumors.

Onalespib selectively binds to Hsp90, thereby inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stability and degradation of many oncogenic signaling proteins and has been used as a biomarker of HSP90 inhibition.