Design, Synthesis and Characterization of Novel and Potent Gamma Secretase Modulators: Physiochemical and Pharmacokinetic Properties


During the past year, our laboratory at UCSD (Wagner laboratory), in close collaboration with the Tanzi laboratory at MGH, discovered, synthesized and characterized (in vitro) a novel series of molecules able to potently prevent the formation of what is currently thought to be the pathogenic culprit of Alzheimer’s disease (AD). Through the use of novel, selective and proprietary chemical substitutions, in conjunction with an arsenal of biochemical screening assays (carried out at both UCSD and MGH), we were able to demonstrate structure activity relationships (SAR) that support these SGSMs as very promising, potent and potentially disease modifying therapeutic agents for AD. The next step in the evaluation of the most potent and with the best aqueous solubility or the most water soluble SGSMs, which would be the focus of year two of the CAF-funded project, will entail a thorough pharmacological or in vivo examination of these molecules in order to identify the best or the “lead” drug candidate.

Funding to Date



Drug Development, Preclinical Drug Development


Steven L. Wagner, Ph.D.

William C. Mobley, M.D., Ph.D.