UCSD-779690

UCSD-779690 is a potent, small-molecule gamma-secretase modulator (GSM) being developed for the prevention and treatment of Alzheimer's disease, particularly early-onset familial Alzheimer's disease (EOFAD). Unlike gamma-secretase inhibitors (GSIs), which block the enzyme's activity and interfere with Notch signaling, UCSD-779690 allosterically modulates the gamma-secretase complex. This modulation shifts the cleavage of amyloid precursor protein (APP) to reduce the production of the neurotoxic amyloid-beta 42 (Aβ42) and Aβ40 peptides while increasing the production of shorter, non-amyloidogenic peptides like Aβ38 and Aβ37. Preclinical studies in transgenic mice, rats, and cynomolgus monkeys have demonstrated its ability to cross the blood-brain barrier and significantly lower brain Aβ42 levels with a favorable safety profile and a wide therapeutic margin.