Paper - WANFANG MED ONLINE

You Position: Home > Paper

The signal transduction pathway of multi-target kinase inhibitors as anticancer agents in clinical use or in phase Ⅲ

( views:21, downloads:0 )

Author:: No author available

Journal Title:: ACTA PHARMACEUTICA SINICA

Issue:: 3

DOI:: 10.3321/j.issn:0513-4870.2009.03.005

Key Word:: 肿瘤;多靶点;激酶抑制剂;信号传导通路;抗肿瘤药物

Abstract：细胞的信号传导在细胞的代谢、分化以及死亡的过程中起着重要的作用.肿瘤的发生和发展与细胞信号的过度表达有关.以蛋白激酶为靶点的抗肿瘤治疗现已成为肿瘤研究中十分活跃的领域.目前作为抗癌药物已经上市及正在临床开发中的激酶抑制剂多数为多靶点抑制剂.多靶点激酶抑制剂能够同时抑制多个细胞信号转导通路,从而使得肿瘤细胞在多个方面受到抑制.多靶点激酶抑制剂在疗效和控制耐受性方面具有一定的优势.本文对已经上市及部分正在Ⅲ期临床开发中的多靶点激酶抑制剂的抑酶谱及其信号传导通路进行综述分析.

Reference

[1]王芳,符立梧.多靶点抗肿瘤新药索拉非尼的研究进展[J].2008,(8).
[2]杨健,陈增良.血管新生与肿瘤生长的研究进展[J].2001,(4).
[3]陆舜,李子明,成柏君,等.厄洛替尼治疗复治晚期非小细胞肺癌的临床分析[J].2007,(9).
[4]Mangum S,Bremer TM,Burris H 3rd,etc.Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies.[J].2005,23(11).
[5]Alexander Levitzki.Targeting signal transduction for disease therapy[J].1997,14(2).
[6]Cowan Jacob S,Mestan J,Manley P,etc.AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL.[J].2006,94(12).
[7]Scherubl H,Schuppan D,Baradari V,etc.Sorafenib alone or as combination therapy for growth control of cholangiocarcinoma.[J].2007,73(9).
[8]Tai YT,Yasui H,Podar K,etc.The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma[J].2006,103(51).
[9]Lyons AB,Blake S,Hughes TP,etc.The Src/ABL kinase inhibitor dasatinib (BMS-354825) inhibits function of normal human T-lymphocytes in vitro.[J].2008,127(3).
[10]Minelli A,Bracarda S,Caserta C,etc.Targeting of EGFR tyrosine kinase by ZD1839 ("Iressa") in androgen-responsive prostate cancer in vitro.[J].2006,88(2).
[11]Rahmani M,Grant S,Davis EM,etc.Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells involves down-regulation of Mcl-1 through inhibition of translation[J].2005,280(42).
[12]E, Buchdunger,J, Zimmermann,H, Mett,etc.Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative.[J].1996,56.
[13]Kudlacz E,Conklyn M,Andresen C,etc.The JAK-3 inhibitor CP-690550 is a potent anti-inflammatory agent in a murine model of pulmonary eosinophilia.[J].2008,582(1).
[14]Advani AnjaliS,Pendergast AnnMarie.Bcr-Abl variants: biological and clinical aspects.[J].2002,26(8).
[15]Owens G,Xia W,Mullin RJ,etc.Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways.[J].2002,21(41).
[16]Callahan L,Hall Meyers E,Wright RD,etc.Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl.[J].2005,7(2).
[17]de Bono JS,Rowinsky EK.The ErbB receptor family: a therapeutic target for cancer.[J].2002,8(4 Suppl.).
[18]Bold G,Wood J,Huth A,etc.Anthranilic Acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors.[J].2002,45(26).
[19]Komander D,Kular GS,Schuttelkopf AW,etc.Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1[J].2004,12(2).
[20]Hudes GR,Michaelson MD,Bolte O,etc.Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study.[J].2007,8(11).
[21]Millward MJ,Wang Y,Copeman M,etc.The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study.[J].2006,95(7).
[22]Hutson TE,Sonpavde G.Pazopanib: a novel multitargeted tyrosine kinase inhibitor.[J].2007,9(2).
[23]Deguchi Y,Kimura S,Fujiyama Y,etc.Comparison of imatinib, dasatinib, nilotinib and INNO-406 in imatinib-resistant cell lines.[J].2008,32(6).
[24]Thavasu P,Balkwill F,Twelves C,etc.Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C.[J].2001,19(5).
[25]Wang DH,Henry RG,Pallavicini MG,etc.AG-013736, a novel inhibitor of VEGF receptor tyrosine kinases, inhibits breast cancer growth and decreases vascular permeability as detected by dynamic contrast-enhanced magnetic resonance imaging[J].2007,25(3).
[26]Steinberg M.Dasatinib: a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia.[J].2007,29(11).
[27]Imming P,Sinning C,Meyer A.Drugs, their targets and the nature and number of drug targets.[J].2006,5(10).
[28]Kantarjian H,Giles F,Wunderle L,etc.Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL.[J].2006,354(24).
[29]Faivre S,Sargent W,Raymond E,etc.Molecular basis for sunitinib efficacy and future clinical development.[J].2007,6(9).
[30]Czechowska A,Drzewoski J,Poplawski T,etc.Imatinib (STI571) induces DNA damage in BCR/ABL-expressing leukemic cells but not in normal lymphocytes.[J].2005,152(2).
[31]Lanzi C,Nicolini V,Cassinelli G,etc.Targeting RET for thyroid cancer therapy.[J].2009,77(3).
[32]Bilanges B,Torbett N,Vanhaesebroeck B.Killing two kinase families with one stone[J].2008,4(11).
[33]B M, Trost,W, Tang.An enantioselective strategy to macrocyclic bisindolylmaleimides. An efficient formal synthesis of LY 333531.[J].2001,3(21).