In Vitro: MRK-560 (30, 100, 300, 1000 nM; 15days) blocks mutant NOTCH1 receptor signaling in human T-ALL cell lines.
In Vivo: MRK-560 (15.54 mg/kg; S.C.; single daily for 14 days) shows strong antileukemic effects on T-ALL model. MRK-560 (1, 3, 10, 30, 100 mg/kg; p.o.; single) shows good blood-brain barrier permeability in a dose-dependent manner in rats.
MRK-560 (1, 3, 10, 30, 100 mg/kg; p.o.; single) inhibits the production of Aβ levels in brain and cerebrospinal fluid. MRK-560 (1 mg/kg; p.o.; single) shows a good bioavailability of 70 to 90%, and Tmax is 12 h. MRK-560 (1 mg/kg; i.v.; single) is suitable for once-a-day dosing (with a low plasma clearance and a half-life of more than 15 h).