MK-0752 is a potent gamma secretase (¦Ã-secretase) inhibitor in clinical development with an IC50 of 5 nM for A¦Â40 in human SH-SY5Y cells.Defining the metabolic fate of amyloid precursor protein (APP) in the central nerve system (CNS) is critically important for the development of ¦Ã-secretase inhibitors to treat Alzheimer¡¯s disease (AD), as a substrate build-up of APP fragments could potentially lead to an overshoot in neurotoxic amyloid peptides. The lack of A¦Â rebound in the CNS could be attributed to the shunting of APP (possibly beta C-terminal fragments, e.g. C99) to ¦Ã-secretase independent degradation. MK-0752 reduced A¦Â40 in a dose-dependent manner. Dose-dependent reductions in plasma, brain and CSF A¦Â40 were observed in guinea-pigs following single oral doses of 10¨C30 mg/kg (brain IC50 = 0.44 ¦ÌM). Concentration required for 50 percent reduction of brain A¦Â40 was 318 nM and 0.15 ¦ÌM in APP-YAC and Tg2576 mice, respectively.

June 21, 2017

prudect name : MK-0752 is a potent gamma secretase (¦Ã-secretase) inhibitor in clinical development with an IC50 of 5 nM for A¦Â40 in human SH-SY5Y cells.Defining the metabolic fate of amyloid precursor protein (APP) in the central nerve system (CNS) is critically important for the development of ¦Ã-secretase inhibitors to treat Alzheimer¡¯s disease (AD), as a substrate build-up of APP fragments could potentially lead to an overshoot in neurotoxic amyloid peptides. The lack of A¦Â rebound in the CNS could be attributed to the shunting of APP (possibly beta C-terminal fragments, e.g. C99) to ¦Ã-secretase independent degradation. MK-0752 reduced A¦Â40 in a dose-dependent manner. Dose-dependent reductions in plasma, brain and CSF A¦Â40 were observed in guinea-pigs following single oral doses of 10¨C30 mg/kg (brain IC50 = 0.44 ¦ÌM). Concentration required for 50 percent reduction of brain A¦Â40 was 318 nM and 0.15 ¦ÌM in APP-YAC and Tg2576 mice, respectively.
MK-0752

Synonyms: CAS NO: 471905-41-6 or 952578-68-6Molecular Formula: C21H21ClF2O4SMolecular Weight: 442.9Purity: 98% minSolubility: In DMSOStorage: −20°C


web site: www.medchemexpress.com

References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18525354