Description
LY-450139 is a γ-secretase inhibitor that suppresses Notch signaling and exhibits neuroprotective activity. LY-450139 displays mixed results in clinical trials as a potential treatment for Alzheimer’s disease. This compound also increases glutamate in the prefrontal cortex when administered chronically and activates growth hormone secretagogue receptor GHS-R1a.
References
Beggiato S, Giuliani A, Sivilia S, et al. CHF5074 and LY450139 sub-acute treatments differently affect cortical extracellular glutamate levels in pre-plaque Tg2576 mice. Neuroscience. 2014 Apr 25;266:13-22. PMID: 24530449.
Doody RS, Raman R, Farlow M, et al. A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013 Jul 25;369(4):341-50. PMID: 23883379.
Schellekens H, McNamara O, Dinan TG, et al. Semagacestat, a γ-secretase inhibitor, activates the growth hormone secretagogue (GHS-R1a) receptor. J Pharm Pharmacol. 2013 Apr;65(4):528-38. PMID: 23488781.