- Ganetespib is a non-geldamycin synthetic inhibitor of Hsp90 that has demonstrated activity against multiple cancer cell lines and tumor xenografts in preclinical models. Inhibiting the Hsp90 chaperone complex results in the recruitment of ubiquitin ligases, polyubiquination, and proteosomal degradation of Hsp90 client proteins, including transcription factors and proteins involved in angiogenesis (VEGF, VEGFR, HIF-1, STAT-3); growth factor independence (RAF, EGFR,Her2, IGFR); resistance to anti-growth signals (CDK4); tissue invasion and metastases (MET, MMP2); and avoidance of apoptosis (AKT, RIP, Survivin, Bcl-2).