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研究生:吳欣蓉
研究生(外文):Xin-Rung Wu
論文名稱:設計並合成新穎的AMP-activated protein kinase活化劑
論文名稱(外文):Design and synthesis of novel AMP-activated protein kinase activators
指導教授:蕭崇瑋
指導教授(外文):Chung-Wai Shiau
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生物藥學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:23
中文關鍵詞:
相關次數:
  • 被引用被引用:0
  • 點閱點閱:48
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  • 下載下載:0
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中文摘要………….………………………………………………………………….. i
英文摘要..…………………………………………………………………………ii
目錄…………………………………………………………………...………………iii
圖目錄………………..………………………………………………………………iv
表目錄……………………………..………………………………………………... v
第一章緒論……………………………………...…………………………………….7
第一節 乳癌治療策略
第二節 分析CDK4/6抑制劑的結構骨架
第三節 Palbocicilib抗癌作用有來自於其他途徑
第四節 Palbociclib類似物GP-1非透過抑制CDK4/6活性抑制乳癌細胞生長
第五節 AMPK及其下游調節
第六節 AMPK與乳癌的相關性
第二章 研究目標及設計概念……………….……………………………………...14
第一節 探討Palbociclib結構活性相關分析 (Structure-activity relationship, SAR)
第二節 GP-1藉由活化AMPK抑制TNBC細胞株生長
第三節 化學修飾設計概念
第三章 實驗材料與方法…………………………………………………………....16
第一節 藥品及儀器
第二節 化合物的純化與鑑定
第三節 化學修飾設計概念
第四章 研究結果………………………………………………………………........18
第一節 Palbociclib 衍生物之化學合成
第二節 討論
第五章 結論………………………………………………………………………....20
第六章 參考文獻…………………………………………………………...………21

圖目錄
圖一、在肝癌細胞中Palbociclib會活化AMPK及提升ULK1的磷酸化……...…9圖二、GP-1與Palbociclib抑制CDK4/6 kinase activity的比較………………………9 圖三、Palbociclib可以減少Rb磷酸化並且增加AMPK磷酸化…………………..9
圖四、Palbociclib與GP-1增加AMPK磷酸化的比較……………………………...10
圖五、GP-1提升MDA-MB-231 AMPK磷酸化以及減少mTOR下游路徑目標磷酸化…………………………………………………………………………………..11圖六、AMPK序列及結構圖………………………………………………………...12
圖七、Palbociclib與CDK6的共結晶結構圖(紅色虛線箭頭為氫鍵)……………13
圖八、Palladium 介導的2-氯-嘧啶(2-chloro-pyrimidine)胺化反應…………….19


表目錄
表一、乳癌分型及治療方式…………………………………………………………..7
表二、GP-1與Palbociclib抑制兩種三陰性乳癌細胞生長的比較………………...10
表三、先前已合成的GP系列有效化合物…….........................................................12
表四、起始物名稱資訊……………………………………………………………..16
表五、溶劑名稱資訊………………………………………………………………..19
表六、藥品名稱資訊………………………………………………………………..20
表七、GP系列化合物………………………………………………………………..23
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