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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Exhibition Hall 2+3 |
| Time |
10월 19일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-322 |
| Subject |
Synthesis of Novel Tau Aggregation Inhibitors for the Treatment of Alzheimer’s Disease
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| Authors |
GUNHEE KIM, Ae Nim Pae1,*, SANG MIN LIM2,*, Haeun Lee3, WooSeung Son4
Department of Chemistry, Kyung Hee University, Korea
1Korea Institute of Science and Technology, Korea
2Center for Neuromedicine, Korea Institute of Science and Technology, Korea
3Biochemistry, Korea Institute of Science and Technology, Korea
4Department of Chemistry, Yonsei University, Korea
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| 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.
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| E-mail |
gunn.heee@gmail.com |
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120th General Meeting of the KCS