MRK-560

Research use only, not for human use.

MRK-560 is an effective and brain-penetrant inhibitor of γ-secretase.

MRK-560 is an effective and brain-penetrant inhibitor of γ-secretase.

MRK-560 (30, 100, 300, 1000 nM; 15days) blocks mutant NOTCH1 receptor signaling in human T-ALL cell lines.Cell Proliferation Assay Cell Line:HPB-ALL, DND-41, and Jurkat cells Concentration:30, 100, 300, 1000 nM Incubation Time:15 days Result:Reduced NICD1 generation in cells and resulted in a dose-dependent decrease of proliferation in HPB-ALL and DND-41, which depend on NOTCH signaling for their survival.

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). Animal Model:Tg (HLA-DRB1) 31Dmz/Szj (NSG) mice (T-ALL (T cell acute lymphoblastic leukemia) model).Dosage:15.54 mg/kg Administration:Subcutaneous injection; single daily for 14 days. Result:Resulted in strong antileukemic effects and improved median survival to 30 days compared to 18 days in vehicle-treated mice.Animal Model:Male Sprague-Dawley rats (250-300 g).Dosage:1, 3, 10, 30, 100 mg/kg Administration:Oral administration; single (experiment is performed 8 h later)Result:Increased the plasma and brain concentrations in a dose-dependent manner.Reduced (dose-dependent) both brain and CSF Aβ levels, with essentially complete inhibition of the production of both peptides being observed at a dose of 100 mg/kg.Animal Model:Male Sprague-Dawley rats (250-300 g).Dosage:1 mg/kg Administration:Intravenously and orally administration; single.Result:Showed Tmax after the oral dose was 12 h,and bioavailability was 70 to 90%.Revealed a low plasma clearance of less than 5 mL/min/kg with a volume of distribution of approximately 6 L/kg, which translated to a long half-life of more than 15 h.

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Neuroscience

Gamma-secretase

KEAP1-Nrf2

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677772-84-8

517.91

C19H17ClF5NO4S2

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (193.08 mM)

Fc1ccc(F)c(c1)[C@]1(CC[C@@H](CC1)NS(=O)(=O)C(F)(F)F)S(=O)(=O)c1ccc(Cl)cc1

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(-20℃)

With Ice Pack

≥ 2 years