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Alzheimer's disease (AD)

g-Secretase; b-amyloid 42

In vitro and mouse studies identified metabolically stable g-secretase modulators that could help treat familial AD. In vitro, triterpene-based g-secretase modulators with carbamate or ester replacements at the C24 position inhibited pathogenic b-amyloid 42 and showed selectivity over b-amyloid 40. In mice, two of the compounds showed favorable pharmacokinetic and pharmacodynamic profiles and had blood brain barrier penetration, and decreased b-amyloid 42 levels in the brain compared with vehicle control. Next steps include safety studies on similar compounds.
Satori Pharmaceuticals Inc. has g-secretase inhibitors in preclinical testing to treat AD. At least six other companies have g-secretase inhibitors in clinical and preclinical development to treat AD.

SciBX 5(42); doi:10.1038/scibx.2012.1117
Published online Oct. 25, 2012

Patent applications filed; available for licensing

Hubbs, J.L. et al. J. Exp. Med.; published online Oct. 3, 2012;
Contact: Jed L. Hubbs, Satori Pharmaceuticals Inc., Cambridge, Mass.