tcsc0912 Alvespimycin

Alvespimycin is a potent inhibitor of Hsp90, binding to Hsp90 with an EC₅₀ of 62 ± 29 nM.

IC50 & Target: EC50: 62 nM (Hsp90)^[1]

In Vitro: Alvespimycin is a potent inhibitor of Hsp90, binding to Hsp90 with an EC₅₀ of 62 nM. Alvespimycin (17-DMAG) inhibits the growth of the human cancer cell lines SKBR3 and SKOV3, which overexpress Hsp90 client protein Her2, and causes down-regulation of Her2 as well as induction of Hsp70 consistent with Hsp90 inhibition, for Her2 degradation with EC₅₀ of 8 ± 4 nM and 46 ± 24 nM in SKBR3 and SKOV3 cells, respectively; for Hsp70 induction with EC₅₀ of 4 ± 2 nM and 14 ± 7 nM in SKBR3 and SKOV3 cells, respectively^[1]. Compared with the vehicle control, Alvespimycin dose-dependent apoptosis (P<0.001 averaged across 24- and 48-hour time points) at concentrations of 50 nM to 500 nM, which represent pharmacologically attainable doses. Similar to many other agents, Alvespimycin also demonstrates time-dependent apoptosis (P <0.001, averaged across all doses) in chronic lymphocytic leukemia (CLL) cells with extended exposure from 24 to 48 hours. In addition, Alvespimycin is much more potent after 24 and 48 hours of treatment than 17-AAG^[2].

In Vivo: The tumors are grown for two months before the start of i.p. injections every four days over one month with 0, 50, 100 and 200 mg/kg dipalmitoyl-radicicol or 0, 5, 10 and 20 mg/kg Alvespimycin. Despite sample heterogeneity, the HSP90 inhibitor-treated animals have significantly lower tumour volumes than the vehicle control-treated animals. HSP90 inhibitors have been shown to cause liver toxicity in an animal model of gastrointestinal cancer. Nevertheless, the reduction in tumor size using dipalmitoyl-radicicol is statistically significant at 100 mg/kg, while Alvespimycin at either 10 or 20 mg/kg elicits a significant reduction in tumor size^[3].