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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Exhibition Hall 2 |
| Time |
4월 18일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-398 |
| Subject |
Development of Novel Tau Aggregation Inhibitors for the Treatment of Alzheimer's Disease |
| Authors |
Hye Yeon Lee, Haeun Lee1, WooSeung Son2, Ae Nim Pae3, Hak Joong Kim*, Sang Min Lim3,*
Department of Chemistry, Korea University, Korea
1Biochemistry, Korea University of Science and Technology, Korea
2Department of Chemistry, Yonsei University, Korea
3Korea Institute of Science and Technology, Korea
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| Abstract |
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and becomes a serious problem in an aging society. Tau is a microtubule-associated protein and is believed to play an important role in AD pathology. Tau protein binds to microtubules and helps stabilize neuronal microtubules. However, hyperphosphorylation of tau causes dissociation from microtubules, and detached tau proteins tend to self-assemble eventually forming paired helical filaments (PHFs) and neurofibriliary tangles (NFTs). Finally, these PHFs and NFTs can induce neurodegeneration leading to diseases like AD.
Despite the importance of treatment of AD, there are drugs that only alleviates some of the symptoms of AD. Therefore, we pay attention to the pathological characters of tau protein, and intend to develop tau aggregation inhibitors to find disease-modifying drug candidates for AD therapy. To discover new lead compounds that can inhibit tau aggregation, we performed a high-throughput screening based on a Bi-FC assay with in-house libraries. Thereafter, by modifying hit compounds, we found compounds that are more potent and less toxic than Methylene blue: a well-known in vitro tau aggregation inhibitor. Currently, we have synthesized a variety of derivatives through a structure-activity relationship study to find compounds that are more potent than the hit compounds. We are also trying to find potent compounds possessing novel scaffolds by introducing bioisosteres. We will continue our efforts to optimize potency as well as physicochemical properties to develop non-clinical candidates for AD. |
| E-mail |
lhy7390@kist.re.kr |
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123rd General Meeting of the KCS