AT13387

AT13387 is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. (In Vitro) :Onalespib (Compound 35) is a potent inhibitor of Hsp90, with Kd of 0.71 nM. Onalespib shows potent antiproliferative activity in HCT116 cells, with an IC50 of 31 nM. Onalespib also strongly inhibits the proliferation of a panel of human tumor cell lines, showing IC50 of < 100 nM. Onalespib exhibits cytotoxic activity against many of the PPTP cell lines, with median IC50 of 41 nM. (In Vivo) :Onalespib (60 mg/kg, ip 3 days on and 3 days off for four cycles) shows antitumor activity in nude BALB/c mice bearing early stage HCT116 human colon carcinoma xenografts. Onalespib (40 or 60 mg/kg, i.p.) induces significant differences in EFS distribution compared to controls in 17% evaluable solid tumor xenografts, but in none of the ALL xenografts.