| 体内研究: |
Vevorisertib trihydrochloride (25, 50 and 75 mg/kg; p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days) shows potent tumor growth inhibition of 68, 78 and 98%, respectively. Vevorisertib trihydrochloride (5, 10, 20, 40, 80, and 120 mg/kg; p.o. daily for ten days) shows tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively. Vevorisertib trihydrochloride reachs Cmax plasma concentrations of ≥2 μM. Vevorisertib trihydrochloride is generally well-tolerated at dose levels up to 120 mg/kg. Vevorisertib trihydrochloride (MK-4440)/IM combination shows superior efficacy in an IM-sensitive preclinical model of GIST compared with either single agent. |