119th General Meeting of the KCS

Type Poster Presentation
Area 의약화학
Room No. 포스터발표장
Time 4월 20일 (목요일) 11:00~12:30
Code MEDI.P-435
Subject Development of Tau Aggregation Inhibitors for Treatment of Alzheimer’s Disease
Authors 이하은, 배애님1,*, 임상민2
UST 생물화학, Korea
1한국과학기술연구원(KIST) 생체과학연구본부, Korea
2한국과학기술연구원(KIST) 뇌의약연구단, Korea
Abstract Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and becomes a severe problem in an aging society. Tau protein plays an important role in AD pathology. Tau is a microtubule-associated protein and, helps to stabilize neuronal microtubule. But hyperphosphorylation of tau leads to disengage it from the microtubule, which results in self-assembly of tau forming paired helical filaments (PHFs) and neurofibrillary tangles (NFTs). Finally, these PHFs and NFTs induce neuronal damage like AD. Although tauopathy has been extensively studied as a key hypothesis in AD there are no clinical drugs to give the noticeable improvement. Therefore, we study to find Tau-directed therapeutic drug candidates for the treatment of AD, especially, tau aggregation inhibitors. To discover new lead compounds that can inhibit tau aggregation, we performed a high-throughput screening based on Bi-FC assay with in-house and commercial compound libraries. Subsequently, we found hit compounds that are more potent and less toxic than the Methylene blue: a well-known in vitro tau aggregation inhibitor. Currently, a variety of derivatives were synthesized through a structure-activity relationship study to find compounds that are more potent and possess novel scaffolds than the hit compounds. We will continue to work to further optimize potency as well as physicochemical properties to develop clinical candidates.
E-mail h16010@kist.re.kr