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|
| Type |
Poster Presentation |
| Area |
Life Chemistry |
| Room No. |
Exhibition Hall 2 |
| Time |
4월 19일 (금요일) 11:00~12:30 |
| Code |
LIFE.P-377 |
| Subject |
Development of Selective S1P1 Receptor Agonists for Treatment of Multiple Sclerosis |
| Authors |
Eun Ji Cha, Yong Seo Cho1, Ki Duk Park2, Sang Min Lim2,*
Department of Chemistry, Korea University, Korea
1Center for Neuromedicine, Korea Institute of Science and Technology, Korea
2Convergence Research Center for DTC, Korea Institute of Science and Technology, Korea
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| Abstract |
Multiple Sclerosis(MS) is an neurodegenerative autoimmune disorder of the central nervous system. The FDA-approved Fingolimod is the first oral drug for relapsing forms of MS.
Following phosphorylation in vivo, an active form of fingolimod, acts as a sphingosine 1-phosphate(S1P) receptor modulator, binding with high affinity to S1P receptors(S1P1,3~5). Fingolimod causes many side effects such as bradycardia, hypertension, skin cancer, and macular edema due to non-selective binding. As a cause of bradycardia, a GIRK channel activated by G protein pathway signaling due to binding with S1P1 was suggested. The need for the development of S1P1 receptors which act as a β-arrestin pathway, has been suggested in order to avoid side effects caused by the G protein pathway.
A total of 33 compounds were synthesized using five schemes, and Ca2+, β-arrestin and internalization assays were performed. Compounds that show efficacy as therapeutic agents have not been elucidated, but will be used to discuss and improve the results. |
| E-mail |
ijnueahc@naver.com |
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123rd General Meeting of the KCS