MRK-560_product_DataBase

Bioactivity

MRK-560 is an orally active, brain barrier-penetrating γ-Secretase inhibitor, can potently reduces Aβ peptide in rat brain and cerebrospinal fluid. MRK-560 also 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].

Invitro

MRK-560 (30, 100, 300, 1000 nM; 15days) blocks mutant NOTCH1 receptor signaling in human T-ALL cell lines[1]. Cell Proliferation Assay[1] Cell Line:

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 Tmax 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]. Animal Model:

Name

MRK-560

CAS

677772-84-8

Formula

C19H17ClF5NO4S2

Molar Mass

517.92

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Habets RA, et al. Safe targeting of T cell acute lymphoblastic leukemia by pathology-specific NOTCH inhibition. Sci Transl Med. 2019 May 29;11(494):eaau6246. [2]. Best JD, et al. In vivo characterization of Abeta(40) changes in brain and cerebrospinal fluid using the novel gamma-secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) in t

PeptideDB

MRK-560

CAS: 677772-84-8 F: C19H17ClF5NO4S2 W: 517.92