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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Event Hall |
| Time |
4월 19일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-586 |
| Subject |
Synthesis of Novel Tau Aggregation inhibitor for the Treatment of Alzheimer’s Disease
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| Authors |
HyoJin Kim, Ae Nim Pae1, Cheol-Hong Cheon*, SANG MIN LIM1,*
Department of Chemistry, Korea University, Korea
1Korea Institute of Science and Technology, Korea
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| Abstract |
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and it is a disease that must be studied because it becomes a serious problem in an aging society. Although tau protein is believed to play an important role in AD and tauopathy has been extensively studied, there are only drugs that alleviate some of the symptoms of Alzheimer's disease, and there are no disease-modifying drugs. Tau is a microtubule-associated protein (MAP) that binds to microtubules and helps stabilize microtubules. However, hyperphosphorylation of tau induces detachment from microtubules, and detached tau tends to self-aggregate forming paired helical filaments (PHFs) and neurofibrillary tangles (NFTs) which induce neurodegeneration leading to diseases such as AD. Therefore, we develop tau aggregation inhibitors to find drug candidates for the treatment of AD. To discover new hit compounds that can inhibit tau aggregation, we performed a high-throughput screening based on Bi-FC assay with in-house and commercial compound libraries. By modifying hit compounds, we have found compounds that are more potent and less toxic than Methylene blue: a well-known in vitro tau aggregation inhibitor. Currently, a variety of derivatives have been synthesized through a structure-activity relationship study to find compounds that are more potent than the hit compounds. We also try to find potent compounds possessing novel scaffolds by scaffold hopping or introduction of bioisosters. We will continue to work to further optimize potency as well as physicochemical properties to develop clinical candidates. |
| E-mail |
t16895@kist.re.kr |
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121st General Meeting of the KCS