STA-1474 is a water soluble prodrug of Ganetespib (STA 9090), which is a potent, second generation small-molecule inhibitor of HSP90 (IC50=4 nM).
STA-1474 promoted loss of cell viability, inhibition of cell proliferation and induction of apoptosis in osteosarcoma (OSA) cell lines.
STA-1474 and its active metabolite STA-9090 also demonstrated increased potency compared to 17-AAG.
STA-1474 exhibited selectivity for OSA cells versus normal canine osteoblasts, and HSP90 co-precipitated with co-chaperones p23 and Hop in canine OSA cells but not in normal canine osteoblasts.
STA-1474 downregulated the expression of p-Met/Met, p-Akt/Akt and p-STAT3.
STA-1474 induced tumor regression, caspase-3 activation and downregulation of p-Met/Met and p-Akt/Akt in OSA xenografts.
