2-((S)-1-((2S,5R)-5-(4-CHLORO-5-FLUORO-2-(TRIFLUOROMETHYL)PHENYL)TETRAHYDROFURAN-2-YL)ETHYL)-7-(4-METHYL-1H-IMIDAZOL-1-YL)-3,4-DIHYDRO-2H-PYRIDO[1,2-A]PYRAZINE-1,6-DIONE

PF-06648671 is a novel, brain‐penetrable, and orally active γ‐secretase modulator (GSM). PF-06648671 reduces Aβ42 and Aβ40, with concomitant increases in Aβ37 and Aβ38 in vitro. PF-06648671 is used for the study of Alzheimer’s disease[1]. In a cell‐based assay, PF‐06648671 reduces Aβ42 and Aβ40 , with concomitant increases in Aβ37 and Aβ38, without inhibiting the cleavage of Notch or other substrates[1]. PF‐06648671 demonstrates reduces Aβ42 within the brain and CSF following acute oral administration in animals[1].

[1]. Jae Eun Ahn, et al. Pharmacokinetic and Pharmacodynamic Effects of a γ-Secretase Modulator, PF-06648671, on CSF Amyloid-β Peptides in Randomized Phase I Studies. Clin Pharmacol Ther 2020 Jan;107(1):211-220.