ELND 007

ELND 007 (Compound 34) is a metabolically stable γ-secretase inhibitor designed to selectively inhibit amyloid beta (Aβ) generation while minimizing Notch inhibition. Developed alongside ELND 006 (Compound 30), it underwent human clinical trials following a synthetic strategy emphasizing diversity and chirality. In preclinical studies, ELND 007 showed promising in vitro and in vivo characteristics, effectively reducing Aβ levels. Comparative studies with other γ-secretase inhibitors like Semagacestat, Begacestat, and Avagacestat highlighted its efficacy in lowering Aβ production, particularly demonstrated by reduced Aβ levels in the cerebrospinal fluid (CSF) of healthy human volunteers, suggesting potential therapeutic benefit for Alzheimer's disease[1].

[1]Discovery of (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch