ELN318463 (racemate)

ELN318463 racemate is the racemate of ELN318463. ELN318463 is an amyloid precursor protein (APP) selective γ-secretase inhibitor. ELN318463 shows differential inhibition of presenilin (PS1)- and PS2-comprised γ-secretase with EC₅₀s of 12nM and 656 nM for PS1and PS2, respectively. ELN318463 is 51-fold more selective for PS1^[1][2]. IC50 & Target: γ-secretase^[1] In Vitro: ELN318463 behaves as a classic γ-secretase inhibitor, demonstrates 75- to 120-fold selectivity for inhibiting Aβ production compared with Notch signaling in cells, and displaces an active site directed inhibitor at very high concentrations only in the presence of substrate^[2]. In Vivo: Brain levels of ELN318463 at 30 mg/kg are 0.754 μM in FVB brains and 0.69 μM in PDAPP brains, and at 100 mg/kg dose the levels were 2.7 μM in FVB brains and 1.87 μM in PDAPP brains. Discordance between Aβ_1-40 and Aβ_x-40 in BACE KO or wild-type BACE inhibitor treated mice has been reported^[1].