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PI3K-mTOR双重小分子抑制剂的研究进展

陈颖 韩进松 王重庆 宋云龙 周永刚 朱驹

陈颖, 韩进松, 王重庆, 宋云龙, 周永刚, 朱驹. PI3K-mTOR双重小分子抑制剂的研究进展[J]. 药学实践与服务, 2014, 32(5): 332-336,359. doi: 10.3969/j.issn.1006-0111.2014.05.004
引用本文: 陈颖, 韩进松, 王重庆, 宋云龙, 周永刚, 朱驹. PI3K-mTOR双重小分子抑制剂的研究进展[J]. 药学实践与服务, 2014, 32(5): 332-336,359. doi: 10.3969/j.issn.1006-0111.2014.05.004
CHEN Ying, HAN Jinsong, WANG Chongqing, SONG Yunlong, ZHOU Yonggang, ZHU Ju. Review of research on dual PI3K-mTOR small molecular inhibitors[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(5): 332-336,359. doi: 10.3969/j.issn.1006-0111.2014.05.004
Citation: CHEN Ying, HAN Jinsong, WANG Chongqing, SONG Yunlong, ZHOU Yonggang, ZHU Ju. Review of research on dual PI3K-mTOR small molecular inhibitors[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(5): 332-336,359. doi: 10.3969/j.issn.1006-0111.2014.05.004

PI3K-mTOR双重小分子抑制剂的研究进展

doi: 10.3969/j.issn.1006-0111.2014.05.004

Review of research on dual PI3K-mTOR small molecular inhibitors

  • 摘要: PI3K脂激酶家族介导的细胞信号转导通路,调节细胞增殖、分化、凋亡等一系列活动,已经成为治疗肿瘤、炎症等疾病的重要靶标。近来出现了多种结构类型的该通路抑制剂,笔者总结了近年内进入临床研究的具有PI3K-mTOR双重抑制活性的小分子化合物。
  • [1] Vivanco I, Sawyers CL, The phosphatidylinositol 3,kinase AKT pathway in human cancer[J]. Nat Rev Cancer, 2002,2(7):489-501.
    [2] Bjornsti MA, Houghton PJ, The TOR pathway:a target for cancer therapy[J]. Nat Rev Cancer, 2004,4(5):335-348.
    [3] Workman P, Clarke PA, Raynaud FI,et al.Drugging the PI3 kinome:from chemical tools to drugs in the clinic[J]. Cancer Res, 2010,70(6):2146-2157.
    [4] Denley A, Kang S, Karst U,et al.Oncogenic signaling of class I PI3K isoforms[J]. Oncogene, 2008, 27(18):2561-2574.
    [5] Falasca M, Maffucci T, Role of class Ⅱ phosphoinositide 3-kinase in cell signalling[J]. Biochem Soc Trans, 2007,35(Pt 2):211-214.
    [6] Guertin DA, Sabatini DM. Defining the role of mTOR in cancer[J]. Cancer Cell, 2007,12(1):9-22.
    [7] Bunney TD, Katan M.Phosphoinositide signalling in cancer:beyond PI3K and PTEN[J]. Nat Rev Cancer, 2010,10(5):342-352.
    [8] Bussink J, van der Kogel AJ, Kaanders JH, Activation of the PI3,K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer[J]. Lancet Oncol, 2008,9(3):288-296.
    [9] Massion PP, Kuo WL, Stokoe D,et al. Genomic copy number analysis of non-small cell lung cancer using array comparative genomic hybridization:implications of the phosphatidylinositol 3-kinase pathway[J]. Cancer Res, 2002,62(13):3636-3640.
    [10] Sutherlin DP, Bao L, Berry M,et al. Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer[J]. J Med Chem, 2011,54(21):7579-7587.
    [11] Wu P, Hu YZ.Small molecules targeting phosphoinositide 3-kinases[J]. Med Chem Comm, 2012,3(11):1337-1355.
    [12] Garlich JR, De P, Dey N,et al. A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity[J]. Cancer Res, 2008,68(1):206-215.
    [13] Ozbay T, Durden DL, Liu T,et al. In vitro evaluation of pan-PI3-kinase inhibitor SF1126 in trastuzumab-sensitive and trastuzumab-resistant HER2-over-expressing breast cancer cells[J]. Cancer Chemother Pharmacol, 2010,65(4):697-706.
    [14] Stauffer F, Maira SM, Furet P,et al. Imidazo[4,5-c]quinolines as inhibitors of the PI3K/PKB-pathway[J]. Bioorg Med Chem Lett, 2008,18(3):1027-1030.
    [15] Knight SD, Adams ND, Burgess JL,et al. Discovery of GSK2126458, a highly potent Inhibitor of PI3K and the mammalian target of rapamycin[J]. Acs Med Chem Lett, 2010,1(1):39-43.
    [16] Venkatesan AM, Dehnhardt CM, Delos SE,et al. Bis(morpholino-1,3,5-triazine)derivatives:potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors:discovery of compound 26(PKI-587), a highly efficacious dual Inhibitor[J]. J Med Chem, 2010,53(6):2636-2645.
    [17] Dehnhardt CM, Venkatesan AM, Delos SE,et al. Lead optimization of N-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors:discovery of PKI-402[J]. J Med Chem, 2010,53(2):798-810.
    [18] Mallon R, Feldberg LR, Lucas J, et al.Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor[J]. Clin Cancer Res, 2011,17(10):3193-3203.
    [19] Cheng HM, Bagrodia S, Bailey S,et al. Discovery of the highly potent PI3K/mTOR dual inhibitor PF-04691502 through structure based drug design[J]. Med Chem Comm, 2010,1(2):139-144.
    [20] Markman B, Tabernero J,Krop I,et al. Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors[J]. Ann Oncol, 2012,23(9):2399-2408.
    [21] Heffron TP, Berry M, Castanedo G,et al. Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor[J]. Bioorg Med Chem Lett, 2010,20(8):2408-2411.
    [22] Kashiyama T, Oda K, Ikeda Y,et al.Antitumor efficacy of DS-7423, a novel PI3K/mTOR dual inhibitor, in ovarian clear cell adenocarcinoma[J]. Eur J Cancer, 2012,48:110-111.
  • [1] 张成中, 朱雪艳, 卜其涛, 王宏瑞, 黄宝康.  基于网络药理学与分子对接预测鸡骨草特征图谱研究 . 药学实践与服务, 2024, 42(7): 1-9. doi: 10.12206/j.issn.2097-2024.202303048
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PI3K-mTOR双重小分子抑制剂的研究进展

doi: 10.3969/j.issn.1006-0111.2014.05.004

摘要: PI3K脂激酶家族介导的细胞信号转导通路,调节细胞增殖、分化、凋亡等一系列活动,已经成为治疗肿瘤、炎症等疾病的重要靶标。近来出现了多种结构类型的该通路抑制剂,笔者总结了近年内进入临床研究的具有PI3K-mTOR双重抑制活性的小分子化合物。

English Abstract

陈颖, 韩进松, 王重庆, 宋云龙, 周永刚, 朱驹. PI3K-mTOR双重小分子抑制剂的研究进展[J]. 药学实践与服务, 2014, 32(5): 332-336,359. doi: 10.3969/j.issn.1006-0111.2014.05.004
引用本文: 陈颖, 韩进松, 王重庆, 宋云龙, 周永刚, 朱驹. PI3K-mTOR双重小分子抑制剂的研究进展[J]. 药学实践与服务, 2014, 32(5): 332-336,359. doi: 10.3969/j.issn.1006-0111.2014.05.004
CHEN Ying, HAN Jinsong, WANG Chongqing, SONG Yunlong, ZHOU Yonggang, ZHU Ju. Review of research on dual PI3K-mTOR small molecular inhibitors[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(5): 332-336,359. doi: 10.3969/j.issn.1006-0111.2014.05.004
Citation: CHEN Ying, HAN Jinsong, WANG Chongqing, SONG Yunlong, ZHOU Yonggang, ZHU Ju. Review of research on dual PI3K-mTOR small molecular inhibitors[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(5): 332-336,359. doi: 10.3969/j.issn.1006-0111.2014.05.004
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