Medicinal Chemistry, Drug Discovery, Preclinical Development, Alzheimer's Disease.
Development of therapeutics for Alzheimer's disease (AD) and other neurodegenerative disorders. Current focus of research in AD includes: (1) discovery of molecules that increase the sAPPα/Aβ42 ratios, a candidate from this class − F03, has advanced into Phase1b/2a trials in subjects with MCI due to AD; (2) discovery of molecules that reverse the ApoE4-mediated risk factor in AD; (3) discovery of APP-selective BACE inhibitors; (4) discovery of CRF receptor modulators that reduce p-Tau and reverse the Aβ induced memory deficits; and (5) discovery of molecules that prevent the intracellular APPΔC31 cleavage as potential therapeutics for AD.
Dr. John is an accomplished medicinal chemist and leads a Drug Discovery & Translational Laboratory at the Department of Neurology at UCLA. Dr. John is a member of the Alzheimer’s Disease Program in the Mary S. Easton Center for Alzheimer's Disease that is under the direction of Professor Dale E. Bredesen, M.D., Augustus Rose Professor of Neurology, Department of Neurology, UCLA, and is the Co-Director of the Alzheimer's Drug Development Network (ADDN), a network that was originally co-founded by Drs. John and Bredesen at the Buck Institute for Research on Aging in Novato. The ADDN represents researchers with basic science and development expertise, and leverages internal and external capabilities with a goal of enabling therapeutic agents to progress from bench to bedside. Previously Dr. John was with Athena Neurosciences and Elan Pharmaceuticals for 18 years where he led a team of medicinal chemists developing drugs for CNS diseases with a focus on AD. His work at Elan included development of potent inhibitors for BACE and γ-secretase, key enzymes in formation Aβ and amyloid plaques. Dr. John is an inventor on over 100 pending or issued patents on compounds and analogs for CNS related targets.