MK-0752 is an orally active, potent and specific inhibitor of γ-secretase, which suppresses the cleavage of γ-secretase substrates such as amyloid precursor protein (APP) and Notch (IC50 ~50 nM). In healthy volunteer studies as well as in a small clinical trial in patients with T-cell acute lymphoblasticleukemia, MK-0752 is generally well tolerated, and GI toxicity is dose limiting [1]. MK-0752 shows dose-dependent reduction of Aβ40 in human SH-SY5Y cells (IC50= 5 nM), and in plasma, brain, and CSF of guinea-pigs following single oral doses of 10-30 mg/kg (brain IC50= 440 nM). In a rhesus monkey cisterna magna ported (CMP) model, MK-0752 not only reduces newly generated CNS Aβ in the brain, but alters levels of noncanonical APP fragments including Aβ 1-14, 1-15, 1-16, and 1-17. This demonstrates an alternative degradation pathway for CNS APP during γ-secretase inhibition [2-3].
Chemical Properties
Cas No.: 471905-41-6
M. Wt.: 442.9
Formula: C21H21ClF2O4S
Purity: >98%
Synonym: MK0752
Chemical Name:cis-3-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]propanoic acid
Solubility: Soluble in DMSO
Storage: Store solid at -20 ºC for the stability of two years.