ELND 006 (Compound 30) is a metabolically stable γ-secretase inhibitor designed to selectively inhibit amyloid beta (Aβ) generation while sparing Notch signaling. It was developed through a synthetic strategy emphasizing diversity and chirality. ELND 006, along with its analog ELND007 (Compound 34), progressed into human clinical trials. In preclinical studies, both compounds demonstrated effective reduction of Aβ levels in vitro and in vivo. Comparisons with other γ-secretase inhibitors like Semagacestat, Begacestat, and Avagacestat underscored their potency and specificity in lowering Aβ levels in cerebrospinal fluid (CSF) of healt human volunteers, suggesting potential therapeutic efficacy in Alzheimer's disease.
References:
[1]. Discovery of (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluorometl)phenylsulfonyl)-4,5-didro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-Cyclopropyl-8-fluoro-5-(6-(trifluorometl)pyridin-3-ylsulfonyl)-4,5-didro-2H-pyrazolo[4,3-c]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch