Small-molecule inhibitor: LY411575

Name

History: LY411575 was described as a potent inhibitor of gamma-secretase by Wong et al. (2004).
Peptidases inhibited: Inhibits the peptidase activity of presenilin 1 in the gamma-secretase complex in vivo (Wong et al., 2004), and in the processing of Notch (Okamoto et al., 2009). Also inhibits impas-1 peptidase (Fuwa et al., 2007).
Mechanism: A photoactivatable, biotinylated derivative has been used to show that LY411575 reacts with the N-terminal fragment of presenilin 1 within the gamma-secretase complex, and also interacts with impas-1 peptidase (Fuwa et al., 2007).

Structure
Chemical/biochemical name: N(2)-[(2S)-2-(3,5->difluorophenyl)-2-hydroxyethanoyl]-N(1)-[(7S)-5-methyl- 6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide
Related inhibitors: The compound LY-D is a less active diastereoisomer of LY411575 (Wong et al., 2004).

Synthesis: Multi-gram chemical synthesis of LY411575 was described by Fauq et al. (2007).