MRK-560

MRK-560 is an orally active, brain barrier-penetrated γ-Secretase inhibitor, reducing Aβ peptide in rat brain and cerebrospinal fluid. MRK-560 decreases mutant NOTCH1 processing by selectively inhibiting PSEN1. MRK-560 can be used in studies of Alzheimer's disease and T-cell acute lymphoblastic leukaemia (T-ALL)^[1][2]. IC50 & Target:γ-secretase, PSEN1^[1][2]. In Vitro:MRK-560 (30, 100, 300, 1000 nM; 15days) blocks mutant NOTCH1 receptor signaling in human T-ALL cell lines^[1]. In Vivo:MRK-560 (15.54 mg/kg; S.C.; single daily for 14 days) shows strong antileukemic effects on T-ALL model^[1].
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^[2].

MRK-560 (1, 3, 10, 30, 100 mg/kg; p.o.; single) inhibits the production of Aβ levels in brain and cerebrospinal fluid^[2].
MRK-560 (1 mg/kg; p.o.; single) shows a good bioavailability of 70 to 90%, and T_max is 12 h^[2].
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)^[2].