DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Hong, Sung-Woo | - |
dc.contributor.advisor | 홍승우 | - |
dc.contributor.author | Hong, Seung-Hee | - |
dc.contributor.author | 홍승희 | - |
dc.date.accessioned | 2015-04-23T02:22:26Z | - |
dc.date.available | 2015-04-23T02:22:26Z | - |
dc.date.issued | 2014 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=568649&flag=dissertation | - |
dc.identifier.uri | http://hdl.handle.net/10203/196458 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 화학과, 2014.2, [ v, 84 p. ] | - |
dc.description.abstract | This thesis is about development of new kinase inhibitors as targeted cancer therapeutics. The research has two main purposes; one is producing new anticancer agent able to overcome resistance, a major problem faced in present clinical treatment and the other is investigating cancer involved bio-mechanism which has not been established clearly from a biological point. Part 1. Discovery of New Benzothiazole-based Derivatives as Potent Breakpoint Cluster Region-Abelson Kinase and T315I Mutant Inhibitors The existence of drug resistance caused by mutations in the break-point cluster region-Abelson tyrosine kinase (BCR-ABL) kinase domain remains a clinical challenge due to limited effective treatment options for chronic myeloid leukemia (CML). Herein we report a novel series of benzothiazole-based inhibitors that are effective against wild-type and T315I mutant BCR-ABL kinases. The original hit compound, nocodazole, was extensively modified through a structure-based drug design strategy, especially by varying the groups at the C2 and C6 positions of the scaffold. In addition, the introduction of water-solubilizing groups at the terminal ethyl group resulted in enhanced physicochemical properties and potency in cellular inhibition. Several compounds inhibited the kinase activity of both wild-type BCR-ABL and the T315I mutant with IC50 values in the picomolar range and exhibited good antiproliferative effects on Ba/F3 cell lines transformed with either wild-type or T315I mutant BCR-ABL. Keywords: break-point cluster region-Abelson tyrosine kinase, chronic myeloid leukemia, benzothaizole, T315I mutation Part 2. Study of Cross Talk between Trk and PI3K with Development of 7-Azaindole-based Inhibitors Having Anticancer and Antiangiogenic Activity As Phosphatidylinositol-3-kinase (PI3K) is a downstream effector of Tropomyosin-related kinase (Trk), two kinases are closely related in cell signal transduction. Each kinase is an important therapeutic target in cancer... | eng |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | Targeted Cancer Therapeutics | - |
dc.subject | 구조기반 약물설계 | - |
dc.subject | 혈관신생반응 | - |
dc.subject | 만성골수성 백혈병 | - |
dc.subject | 키나아제 | - |
dc.subject | 표적 항암제 | - |
dc.subject | kinase | - |
dc.subject | BCR-ABL | - |
dc.subject | PI3K | - |
dc.subject | Trk | - |
dc.subject | chronic myelogenous leukaemia | - |
dc.subject | angiogenesis | - |
dc.subject | structure based drug design | - |
dc.title | Development of new kinase inhibitors as targeted cancer therapeutics | - |
dc.title.alternative | 표적항암제로서 새로운 키나아제 저해제의 개발에 관한 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 568649/325007 | - |
dc.description.department | 한국과학기술원 : 화학과, | - |
dc.identifier.uid | 020088067 | - |
dc.contributor.localauthor | Hong, Sung-Woo | - |
dc.contributor.localauthor | 홍승우 | - |
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