C-MET抑制剂的研究进展
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摘要
C-MET是由C-MET原癌基因编码的蛋白质,它参与了多种肿瘤的形成、转移和侵袭。C-MET抑制剂是一种非常具有挑战性的新型抗肿瘤药物,它是针对C-MET信号通路治疗肿瘤的研发产物,且基于此靶点的上市药品并不多见,。我们通过集C-MET抑制剂近年在国内的研究进展,综述其在国内的设计开发理念及活性筛选成果,探讨其在国内的未来前景。
C- MET is a kind of protein that participates in a variety of tumor formation,metastasis and invasion,it is coded by C- MET proto- oncogene. C- MET inhibitor is a very challenging anticancer drugs,which is cure the cancer by cut the C- MET signaling pathway,and there is only one listed drug of C- MET inhibitor in the world. We collect all the research progress of C- MET inhibitor in recent years,review its design and development concepts and activity screening achievement,discuss its future prospects in China.
C- MET is a kind of protein that participates in a variety of tumor formation,metastasis and invasion,it is coded by C- MET proto- oncogene. C- MET inhibitor is a very challenging anticancer drugs,which is cure the cancer by cut the C- MET signaling pathway,and there is only one listed drug of C- MET inhibitor in the world. We collect all the research progress of C- MET inhibitor in recent years,review its design and development concepts and activity screening achievement,discuss its future prospects in China.
引文
[1]Kyung hee jung,Byung hee park.Progress in cancer therapy targeting C-met signaling pathway[J].Arch Pharm Res,2012;35(4):595-604
[2]于虹,马秀梅.细胞信号转导和肿瘤靶向治疗[J].内蒙古医科大学学报,2008;12(30):163-165
[3]Youles M,Holmes O.Engineering the NK 1 fragment of hepatocyte frowth factor/scatter factor as a met receptor antagonist[J].J.Mol Biol,2008;377(3):616-622
[4]Sattler M,Salgia R.The met axis as a therapeutic target[J].Update Cancer Therapeut,2009;3(3):109-118
[5]Sawada K,Radjabi A,et al.C-met over expression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion[J].Cancer Res,2007;67(4):1670-1679
[6]谢斌,董家鸿.逆转录病毒介导的C-met-小干扰rna抑制肝癌转移的体内研究[J].中华肝脏病杂志,2007;15(5):391-392
[7]马勇政,韦伊芳,药立波,等.Ndrg2调控hgf/C-met通路抑制结肠癌细胞的增殖[J].基础研究,2014;06(19):1479-1482
[8]陈德高,王玉芳.Hgf/C-met信号通路的抗肿瘤治疗进展[J].四川生理科学杂志,2013;35(3):108-112
[9]严家菊,刘靖等以C-met为靶点的酪氨酸激酶抑制剂的研究进展[J].国际药学研究杂志,2012;6:39(3):184-212
[10]Catenacci DV,Henderson L.Durable complete response of metastatic gastric cancer with anti-met therapy foolowed by resistance at recurrence[J].Cancer discov,2011;1(7):573-579
[11]Organ SL,Tsao MS,An overview of the C-met signaling pathway[J].Ther Adv Med Oncol,2011;3(1Suppl):7-19
[12]Neklason DW,Done MW.Activating mutation in met oncogene in familial colorectal cancer[J].BMC Cancer,2011;11(8):424-424
[13]陈燕.针对C-met激酶的小分子抑制剂的研究进展[J].青岛医药,2013;45(3):216-218
[14]Schiering N,Knapp S,Marconi M,et al.Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor C-met and its complex with the microbial alkaloid K-252a[J].Proc Nat Acad Sci USA,2003;100(22):12654-12699
[15]Liu L,Greger J.Novel mechanism of lapatinib resistance in her2-positive breasttumor cells:activation of axl[J].Cancer Res,2009;69(17):6871-6878
[16]严家菊.C-met小分子抑制剂XL880的合成[J].Chinese Journal of New Drugs,2012;21(9):1042-1045
[17]田红,肖桂芝.Tivantinib[J].现代药物与临床,2011;3(26):240-243
[18]Qinhua huang,Ted W.Johnson,et al.Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib[J].Journal of Medicinal Chemistry,2014;57(11):1170-1187
[19]孙爱学.以C-met为靶点的新型抑制剂的设计与合成研究[D].南京:南京理工大学应用化学专业,2014;2(3):18-25
[20]J.Jean cui,Michele mctigue.Discovery of a novel class of exquisitely selective mesenchymal-epithelial transition factor(C-met)protein kinase inhibitors and identification of the clinicalcandidate-2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol(PF-04217903)for the treatment of cancer[J].Med.Chem,2012;30(55):8091-8109
[21]Porter J,Lumb S.Discovery of4-azaindoles as novel inhibitors of C-met kinase[J].Bioorganic And Medicinal Chemistry Letters,2009;19(10):2780-2784
[22]叶连宝.基于C-met靶点的抗肿瘤药物的设计与合成研究[D].广州:南方医科大学药理学专业,2013;3(6):78-83
[23]Chen HD,Yang SP.Trigochinins A-C:three new daphnane-type diterpenes from trigonostemon chinensis[J].Organic Letters,2010;(12):1168-1171
[24]王洁颖.2-吲哚酮类C-met抑制剂化合物的分子设计和活性评价[D].北京:北京工业大学生物医学工程,2013;10(11):138-140
[25]Lv K,Wang L,Lin ML,et al.Synthesis and antitumor activity of5-[1-(3-(dimethylamino)propyl)-5-halogenated-2-oxoindolin-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxamides[J].Bioorganic And Medicinal Chemistry Letters,2011;38(21):3062-3065
[26]Dangelon D,Bellone SF,Booker SK,et al.Design,Synthesis,And biological evaluation of potent C-met inhibitors[J].J Med Chem,2008;51(18):5766-5779
[27]Kung PP,Funk L,Meng J,et al.Structure activity relationships of quinoline-containing C-met inhibitors[J].Eur J Med Chem,2008;43(6):1321-1329
[28]王海勇,王林,杨晓明.基于C-met信号通路的抗癌药物研究进展[J].国外医学药学分册,2007;34(6):401-404
[29]严家菊.多芳类hgf/C-met酪氨酸激酶抑制剂的设计合成与活性研究[D].合肥:安徽医科大学药物化学专业,2012;5(7):89-91
[2]于虹,马秀梅.细胞信号转导和肿瘤靶向治疗[J].内蒙古医科大学学报,2008;12(30):163-165
[3]Youles M,Holmes O.Engineering the NK 1 fragment of hepatocyte frowth factor/scatter factor as a met receptor antagonist[J].J.Mol Biol,2008;377(3):616-622
[4]Sattler M,Salgia R.The met axis as a therapeutic target[J].Update Cancer Therapeut,2009;3(3):109-118
[5]Sawada K,Radjabi A,et al.C-met over expression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion[J].Cancer Res,2007;67(4):1670-1679
[6]谢斌,董家鸿.逆转录病毒介导的C-met-小干扰rna抑制肝癌转移的体内研究[J].中华肝脏病杂志,2007;15(5):391-392
[7]马勇政,韦伊芳,药立波,等.Ndrg2调控hgf/C-met通路抑制结肠癌细胞的增殖[J].基础研究,2014;06(19):1479-1482
[8]陈德高,王玉芳.Hgf/C-met信号通路的抗肿瘤治疗进展[J].四川生理科学杂志,2013;35(3):108-112
[9]严家菊,刘靖等以C-met为靶点的酪氨酸激酶抑制剂的研究进展[J].国际药学研究杂志,2012;6:39(3):184-212
[10]Catenacci DV,Henderson L.Durable complete response of metastatic gastric cancer with anti-met therapy foolowed by resistance at recurrence[J].Cancer discov,2011;1(7):573-579
[11]Organ SL,Tsao MS,An overview of the C-met signaling pathway[J].Ther Adv Med Oncol,2011;3(1Suppl):7-19
[12]Neklason DW,Done MW.Activating mutation in met oncogene in familial colorectal cancer[J].BMC Cancer,2011;11(8):424-424
[13]陈燕.针对C-met激酶的小分子抑制剂的研究进展[J].青岛医药,2013;45(3):216-218
[14]Schiering N,Knapp S,Marconi M,et al.Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor C-met and its complex with the microbial alkaloid K-252a[J].Proc Nat Acad Sci USA,2003;100(22):12654-12699
[15]Liu L,Greger J.Novel mechanism of lapatinib resistance in her2-positive breasttumor cells:activation of axl[J].Cancer Res,2009;69(17):6871-6878
[16]严家菊.C-met小分子抑制剂XL880的合成[J].Chinese Journal of New Drugs,2012;21(9):1042-1045
[17]田红,肖桂芝.Tivantinib[J].现代药物与临床,2011;3(26):240-243
[18]Qinhua huang,Ted W.Johnson,et al.Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib[J].Journal of Medicinal Chemistry,2014;57(11):1170-1187
[19]孙爱学.以C-met为靶点的新型抑制剂的设计与合成研究[D].南京:南京理工大学应用化学专业,2014;2(3):18-25
[20]J.Jean cui,Michele mctigue.Discovery of a novel class of exquisitely selective mesenchymal-epithelial transition factor(C-met)protein kinase inhibitors and identification of the clinicalcandidate-2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol(PF-04217903)for the treatment of cancer[J].Med.Chem,2012;30(55):8091-8109
[21]Porter J,Lumb S.Discovery of4-azaindoles as novel inhibitors of C-met kinase[J].Bioorganic And Medicinal Chemistry Letters,2009;19(10):2780-2784
[22]叶连宝.基于C-met靶点的抗肿瘤药物的设计与合成研究[D].广州:南方医科大学药理学专业,2013;3(6):78-83
[23]Chen HD,Yang SP.Trigochinins A-C:three new daphnane-type diterpenes from trigonostemon chinensis[J].Organic Letters,2010;(12):1168-1171
[24]王洁颖.2-吲哚酮类C-met抑制剂化合物的分子设计和活性评价[D].北京:北京工业大学生物医学工程,2013;10(11):138-140
[25]Lv K,Wang L,Lin ML,et al.Synthesis and antitumor activity of5-[1-(3-(dimethylamino)propyl)-5-halogenated-2-oxoindolin-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxamides[J].Bioorganic And Medicinal Chemistry Letters,2011;38(21):3062-3065
[26]Dangelon D,Bellone SF,Booker SK,et al.Design,Synthesis,And biological evaluation of potent C-met inhibitors[J].J Med Chem,2008;51(18):5766-5779
[27]Kung PP,Funk L,Meng J,et al.Structure activity relationships of quinoline-containing C-met inhibitors[J].Eur J Med Chem,2008;43(6):1321-1329
[28]王海勇,王林,杨晓明.基于C-met信号通路的抗癌药物研究进展[J].国外医学药学分册,2007;34(6):401-404
[29]严家菊.多芳类hgf/C-met酪氨酸激酶抑制剂的设计合成与活性研究[D].合肥:安徽医科大学药物化学专业,2012;5(7):89-91