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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-311 |
| Subject |
Novel dual inhibitors of amyloid beta and tau aggregation for treatment of Alzheimer’s Disease [CAS 포스터상] |
| Authors |
WooSeung Son, GUNHEE KIM1, SANG MIN LIM2, Kyu-Sung Jeong, Ae Nim Pae3,*
Department of Chemistry, Yonsei University, Korea
1Department of Chemistry, Kyung Hee University, Korea
2Center for Neuromedicine, Korea Institute of Science and Technology, Korea
3Korea Institute of Science and Technology, Korea
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| Abstract |
Alzheimer’s disease(AD) is a chronic neurodegenerative disease that is the most common form of dementia. It is still unclear what AD causes, but AD features amyloid plaques(AP) made of amyloid-β and neurofibrillary tangles(NFTs) arising from the hyperphosphorylated tau aggregation in pathology. It is known AP and NFT are neurotoxic that may lead to impairment of brain. In clinical trials, diverse targeting compounds, such as amyloid aggregation inhibitors, β-secretase inhibitors and so on, have been failed to cure AD patients. Therefore, our rationale of dual inhibitors is to reduce the generation of NFT as well as AP that may relate to causes of AD. We obtained hit compound(DTC0100) which inhibits tau aggregation in Bi-FC assay. Then, we optimized to improve the efficacy of tau aggregation inhibition and pharmacokinetic properties. The synthesized DTC0359 showed excellent inhibition of tau aggregation (IC50 = 0.4 µM) and was also lower amyloid-β aggregation (IC50 = 1.0 µM) in vitro as dual inhibitors. Furthermore, DTC0359 significantly decreases both Aβ aggregation in ex-vivo (APP/PS19 mice) and Tau aggregation in ex-vivo (Tau-P301L-BiFC mice). Optimization of pharmacokinetic properties and in vivo study is ongoing. |
| E-mail |
214012@kist.re.kr |
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120th General Meeting of the KCS