SCH 900229

SCH 900229 is a potent, small-molecule, orally administered gamma-secretase inhibitor (GSI) developed by Schering-Plough (later Merck Research Laboratories) for the potential treatment of Alzheimer's disease. It selectively targets Presenilin-1 (PS1), the catalytic subunit of the gamma-secretase complex, with an Aβ40 IC50 of 1.3 nM and approximately 20-fold selectivity for PSEN1 over PSEN2. Belonging to a novel tricyclic (fused bicyclic) bispyran sulfone chemical series, SCH 900229 demonstrated robust amyloid-beta (Aβ)-lowering effects in preclinical animal models. It was advanced into a first-in-human Phase 1 clinical trial in healthy volunteers to evaluate its safety, tolerability, pharmacokinetics, food effect, and relative bioavailability of different capsule formulations, alongside exploratory biomarker assessments of Hes1 and hair-follicle-based Notch signaling. However, development of the compound was discontinued.

Other names

(-)-16