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Drug intelligence / Profile preview
MRK-560
- Development stage
- Preclinical
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
MRK-560 is a highly potent, brain-penetrant, and orally active small molecule inhibitor of gamma-secretase that selectively targets presenilin 1 (PSEN1)-containing gamma-secretase complexes over presenilin 2 (PSEN2)-containing complexes. Originally developed by Merck & Co. for the treatment of Alzheimer's disease, MRK-560 reduces amyloid-beta (Abeta) peptide levels in the brain and cerebrospinal fluid. More recently, it has been investigated preclinically for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) harboring activating NOTCH1 mutations. Unlike broad-spectrum gamma-secretase inhibitors, MRK-560's selectivity for PSEN1 avoids the dose-limiting gastrointestinal toxicities associated with Notch pathway inhibition in healthy tissues, which express both PSEN1 and PSEN2.
- Other names
- MRK 560MRK560MRK-560N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide
02
Targets
GSEC (Gamma-Secretase Complex)PSEN1 (Presenilin 1)
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