^Yaish P, Gazit A, Gilon C, Levitzki A. Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors. Science. 1988, 242 (4880): 933–935. Bibcode:1988Sci...242..933Y. PMID 3263702. doi:10.1126/science.3263702.
^Gazit A, Osherov N, Posner I, Yaish P, Poradosu E, Gilon C, Levitzki A. Tyrphostins. 2. Heterocyclic and alpha-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases. J Med Chem. 1991, 34 (6): 1896–907. PMID 1676428. doi:10.1021/jm00110a022.
^Osherov N, Gazit A, Gilon C, Levitzki A. Selective inhibition of the epidermal growth factor and HER2/neu receptors by tyrphostins. J Biol Chem. 1993, 268 (15): 11134–42. PMID 8098709.
^Anafi M, Gazit A, Zehavi A, Ben-Neriah Y, Levitzki A. Tyrphostin-induced inhibition of p210bcr-abl tyrosine kinase activity induces K562 to differentiate. Blood. 1993, 82 (12): 3524–9. PMID 7505115.
^Meydan N, Grunberger T, Dadi H, Shahar M, Arpaia E, Lapidot Z, Leeder JS, Freedman M, Cohen A, Gazit A, Levitzki A, Roifman CM. Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor. Nature. 1996, 379 (6566): 645–8. Bibcode:1996Natur.379..645M. PMID 8628398. doi:10.1038/379645a0.
^Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996, 2 (5): 561–6. PMID 8616716. doi:10.1038/nm0596-561.
^Strawn LM, McMahon G, App H, Schreck R, Kuchler WR, Longhi MP, Hui TH, Tang C, Levitzki A, Gazit A, Chen I, Keri G, Orfi L, Risau W, Flamme I, Ullrich A, Hirth KP, Shawver LK. Flk-1 as a target for tumor growth inhibition. Cancer Res. 1996, 56 (15): 3540–5. PMID 8758924.
^Posner I, Engel M, Gazit A, Levitzki A. Kinetics of inhibition by tyrphostins of the tyrosine kinase activity of the epidermal growth factor receptor and analysis by a new computer program. Mol. Pharmacol. 1994, 45 (4): 673–83. PMID 8183246.
^Polier; et al. ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system. Nture Chem Biol. 2013, 9 (5): 307–312. PMID 23502424. doi:10.1038/nchembio.1212.
^Levitzki A, Mishani E. Tyrphostins and other tyrosine kinase inhibitors. Annu Rev Biochem. 2006, 75: 93–109. PMID 16756486. doi:10.1146/annurev.biochem.75.103004.142657.
"Chemical structures and known kinase targets for clinically approved kinase inhibitors" Nature.com （页面存档备份，存于互联网档案馆）
十月 23, 2023
酪氨酸激酶抑制劑, 维基百科中的醫學内容仅供参考, 並不能視作專業意見, 如需獲取醫療幫助或意見, 请咨询专业人士, 詳見醫學聲明, tyrosine, kinase, inhibitor, 是能阻斷酪氨酸激酶的藥物, 由於酪氨酸激酶在細胞內擔任許多訊號傳遞的開關, 因此該酶的突變常常引起癌症, 因此通常做為癌症藥物使用, 作用的晶體構造, 圖示為第二代bcr, abl尼罗替尼, 作用在abl激酶, 之上, 尼罗替尼是用來治療慢性骨髓性白血病, 一種血液科惡性疾病的藥物, 也被稱為, tyrphostins, 也就. 维基百科中的醫學内容仅供参考 並不能視作專業意見 如需獲取醫療幫助或意見 请咨询专业人士 詳見醫學聲明 酪氨酸激酶抑制劑 Tyrosine kinase inhibitor TKI 是能阻斷酪氨酸激酶的藥物 由於酪氨酸激酶在細胞內擔任許多訊號傳遞的開關 因此該酶的突變常常引起癌症 酪氨酸激酶抑制劑因此通常做為癌症藥物使用 酪氨酸激酶抑制劑作用的晶體構造 圖示為第二代Bcr Abl酪氨酸激酶抑制劑尼罗替尼 紅 作用在Abl激酶 藍 之上 尼罗替尼是用來治療慢性骨髓性白血病 一種血液科惡性疾病的藥物 酪氨酸激酶抑制劑也被稱為 Tyrphostins 也就是 酪氨酸磷酸化抑制劑 Tyrosine Phosphorylation Inhibitor 的縮寫 起源於一份1988年的論文 1 該論文是第一篇描述抑制表皮生長因子受體 EGFR 之催化活性的文章 該研究也是第一個透過系統性的搜尋而發現針對酪氨酸磷酸化的小分子抑制劑 該抑制劑不干擾其他磷酸化絲氨酸與蘇氨酸的蛋白激酶 也不影響其他具有類似功能的蛋白質 例如胰島素受器的磷酸化結構域 研究更發現儘管各種酪氨酸激酶的結構域都有高度的保留性 即高度相似 設計精良的藥物仍能分辨不同的蛋白質並予以抑制 例如EGFR和HER2 2 3 目录 1 藥物發展 2 藥物機轉 3 參考文獻 4 參見 5 外部連結藥物發展 编辑目前已經開發了許多酪胺酸激酶抑制劑 以作為抗腫瘤藥和白血球抑制劑 4 5 例如被用來治療慢性骨髓性白血病的伊马替尼 Imatinib 6 稍晚有吉非替尼 Gefitinib 和厄洛替尼 Erlotinib 以EGFR作為目標蛋白 利用早期針對VEGF受器的研究所開發的舒尼替尼 Sunitinib 也被用於抑制FGF PDGF VEGF等蛋白 7 藥物機轉 编辑不同的酪氨酸激酶抑制劑有不同的作用方式 抑制劑能和三磷酸腺苷 受質等競爭 也可以透過異位調控引起激酶的構形改變 8 甚至能讓酪氨酸激酶無法接上維持其穩定性的伴護蛋白 Cdc37 Hsp90 進而導致激酶被泛素化並降解 9 原則上 此藥物也能應用在非癌症的增生性疾病 Proliferative disease 及發炎反應上 10 不過目前還沒有類似的應用 參考文獻 编辑 Yaish P Gazit A Gilon C Levitzki A Blocking of EGF dependent cell proliferation by EGF receptor kinase inhibitors Science 1988 242 4880 933 935 Bibcode 1988Sci 242 933Y PMID 3263702 doi 10 1126 science 3263702 Gazit A Osherov N Posner I Yaish P Poradosu E Gilon C Levitzki A Tyrphostins 2 Heterocyclic and alpha substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2 neu tyrosine kinases J Med Chem 1991 34 6 1896 907 PMID 1676428 doi 10 1021 jm00110a022 Osherov N Gazit A Gilon C Levitzki A Selective inhibition of the epidermal growth factor and HER2 neu receptors by tyrphostins J Biol Chem 1993 268 15 11134 42 PMID 8098709 Anafi M Gazit A Zehavi A Ben Neriah Y Levitzki A Tyrphostin induced inhibition of p210bcr abl tyrosine kinase activity induces K562 to differentiate Blood 1993 82 12 3524 9 PMID 7505115 Meydan N Grunberger T Dadi H Shahar M Arpaia E Lapidot Z Leeder JS Freedman M Cohen A Gazit A Levitzki A Roifman CM Inhibition of acute lymphoblastic leukaemia by a Jak 2 inhibitor Nature 1996 379 6566 645 8 Bibcode 1996Natur 379 645M PMID 8628398 doi 10 1038 379645a0 Druker BJ Tamura S Buchdunger E Ohno S Segal GM Fanning S Zimmermann J Lydon NB Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr Abl positive cells Nat Med 1996 2 5 561 6 PMID 8616716 doi 10 1038 nm0596 561 Strawn LM McMahon G App H Schreck R Kuchler WR Longhi MP Hui TH Tang C Levitzki A Gazit A Chen I Keri G Orfi L Risau W Flamme I Ullrich A Hirth KP Shawver LK Flk 1 as a target for tumor growth inhibition Cancer Res 1996 56 15 3540 5 PMID 8758924 Posner I Engel M Gazit A Levitzki A Kinetics of inhibition by tyrphostins of the tyrosine kinase activity of the epidermal growth factor receptor and analysis by a new computer program Mol Pharmacol 1994 45 4 673 83 PMID 8183246 Polier et al ATP competitive inhibitors block protein kinase recruitment to the Hsp90 Cdc37 system Nture Chem Biol 2013 9 5 307 312 PMID 23502424 doi 10 1038 nchembio 1212 Levitzki A Mishani E Tyrphostins and other tyrosine kinase inhibitors Annu Rev Biochem 2006 75 93 109 PMID 16756486 doi 10 1146 annurev biochem 75 103004 142657 參見 编辑Bcr Abl酪胺酸激酶抑制劑 英语 Bcr Abl tyrosine kinase inhibitor 蛋白質激酶抑制劑 英语 Protein kinase inhibitor 生長因子受體 Growth factor receptor 外部連結 编辑醫學主題詞表 MeSH Protein kinase inhibitors IC50 values for common inhibitors KinaseCentral com Chemical structures and known kinase targets for clinically approved kinase inhibitors Nature com 页面存档备份 存于互联网档案馆 取自 https zh wikipedia org w index php title 酪氨酸激酶抑制劑 amp oldid 78977565, 维基百科，wiki，书籍，书籍，图书馆，
