DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Hong, Sungwoo | - |
dc.contributor.advisor | 홍승우 | - |
dc.contributor.author | Shin, Yongje | - |
dc.contributor.author | 신용제 | - |
dc.date.accessioned | 2018-05-23T19:39:40Z | - |
dc.date.available | 2018-05-23T19:39:40Z | - |
dc.date.issued | 2017 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=675884&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/242157 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 화학과, 2017.2,[iv, 77 p. :] | - |
dc.description.abstract | To effectively overcome various problems of drug development process, it is very important to obtain struc-turally diverse & novel scaffolds at the discovery stage. Although the high-throughput screening technology has been widely used for this purpose, it consumes a lot of cost and time with the increased size of a screening library. Therefore, some rational approaches such as structure-based drug design have attracted considerable attention from research groups. Herein, we focused on the development of small molecule inhibitors against 4 biological targets directly or indirectly connected to cancer. First of all, in order to find potent CYP1A2 inhibitor based on natural products, we have developed an efficient method through a palladium-catalyzed C-H activation/carbonylation and consequently identified a frutinone A derivative having a 2-fold higher potency. Moreover, a variety of structure-based drug design techniques which contain de nove design, fragment linking and structure-based virtual screening, efficiently provided both novel $IKK \beta$ inhibitors with an anti-inflammatory effect in cellular levels and potent $GSK3 \beta$ inhibitors with high selectivity for broad kinases. Finally, structure-based virtual screening and docking studies have shown that coumarin scaffold can serve as a new template for the development of fluorescent ALK inhibitors. Taken together, we expect that structure-based drug design could offer us a promising opportunity for discover structurally diverse and novel compounds as a starting point for drug development. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | Structure-based drug design | - |
dc.subject | frutinone A | - |
dc.subject | IKKbeta | - |
dc.subject | GSK3beta | - |
dc.subject | ALK | - |
dc.subject | 구조에 기반한 약물설계 | - |
dc.subject | 프루티논 A | - |
dc.subject | IKK베타 | - |
dc.subject | GSK3베타 | - |
dc.title | Structure-based development of novel small-molecule kinase inhibitors and efficient synthesis of frutinone a derivatives | - |
dc.title.alternative | 구조에 기반한 새로운 저분자 키나아제 저해제의 개발과 프루티논 A 유도체의 효율적 합성에 관한 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :화학과, | - |
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