MK-0752

MK-0752 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 5 nM.IC50 value: 5 nM (reduces Aβ40 production) [1]Target: γ-secretasein vitro: MK-0752 is identified as a moderately potent γ-secretase inhibitor, which reduces Aβ40 in a dose-dependent manner with an IC50 of 5 nM in human SH-SY5Y cells [1]. In vitro, MK-0752 blocks Notch-intracellular domain (ICD) cleavage and its subsequent nuclear translocation [2]. in vivo: MK-0752 (240 mg/kg) reduces the generation of newly produced Aβ with 90% decrease of AUV in the brain of rhesus monkeys. In addition, MK-0752 treatment increases levels of Aβ 1-14, Aβ 1-15, and Aβ 1-16 , while decreases levels of Aβ 1-17 [1]. In guinea-pigs, oral administration of MK-0752 (10 mg/kg -30 mg/kg) results in the dose-dependent reduction of Aβ40 in plasma, brain and cerebrospinal fluid (CSF) with IC50 of 440 nM in brain [2].

Signaling Pathways >> Neuronal Signaling >> γ-secretase

Signaling Pathways >> Stem Cell/Wnt >> γ-secretase

Research Areas >> Neurological Disease

[1]. Cook JJ, et al. Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. J Neurosci, 2010, 30(19), 6743-6750.

[2]. Harrison H, et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res, 2010, 70(2), 709-718.

DAPT (GSI-IX) | RO4929097 | YO-01027 | PF-3084014 | LY-411575 | L-685,458 | Avagacestat | Semagacestat(LY450139) | Z-Ile-Leu-aldehyde | E 2012 | gamma-secretase modulator 1 | NGP555 | BMS 299897 | gamma-secretase modulator 3 | CHF5074