计算了现有的治疗非小细胞肺癌(NSCLC)常见药物的相关参数,总结了以表皮生长因子受体(EGFR)酪氨酸激酶为靶标的药物分子的药效团特征.在Gefitinib的基础上进行了药物分子的组合化学设计,通过虚拟筛选得到了分子对接得分较高的结构分子,并对其进行了预测和模拟.结果表明:新设计筛选出的2种分子在药代动力学和毒性方面优于Gefitinib,在分子动力学过程上和Gefitinib一样稳定.
[1] 贾苗辉, 杨更亮, 杨春柳, 刘智勤, 马正月, 郭兰弟, JIA Miao-hui, YANG Geng-liang, YANG Ohun-liu, LIU Zhi-qin, MA Zheng-yue, GUO Lan-di. 6-F硫色烯并[4, 3-c]吡唑啉的体内抗肿瘤活性 [J]. 河北大学学报（自然科学版） 2009.doi:10.3969/j.issn.1000-1565.2009.05.015
[2] 侯廷军, 朱丽荔, 陈丽蓉, 徐筱杰. EGFR和4-苯胺喹唑啉类抑制剂之间相互作用模式的研究 [J]. 化学学报 2002.doi:10.3321/j.issn:0567-7351.2002.06.013
[3] 郑华, 王敬萍, 孟弃逸, 刘赞, 李宝兰, 朱允中, ZHENG Hua, WANG Jingping, MENG Qiyi, LIU Zan, LI Baolan, ZHU Yunzhong. 吉非替尼(Iressa)在晚期肺腺癌的靶向治疗疗效观察 [J]. 中国肺癌杂志 2007.
[4] 石书芹, 刘志敏, 刘巍, 史健. 静脉输注西妥昔单抗不良反应的观察及护理 [J]. 临床合理用药杂志 2009.doi:10.3969/j.issn.1674-3296.2009.15.099
[5] 朱丽荔, 侯廷军, 陈丽蓉, 徐筱杰. 表皮生长因子受体和抑制剂之间分子对接的研究 [J]. 化学学报 2002.doi:10.3321/j.issn:0567-7351.2002.01.009
[6] 罗俊华, 李娟, LUO Jun-hua, LI Juan. 厄洛替尼治疗老年晚期NSCLC的临床观察 [J]. 肿瘤防治研究 2009.doi:10.3971/j.issn.1000-8578.2009.03.022
[7] Gilmer TM, Cable L, Alligood K, Rusnak D, Spehar G, Gallagher KT, Woldu E, Carter HL, Truesdale AT, Shewchuk L, Wood ER. Impact of common epidermal growth factor receptor and HER2 variants on receptor activity and inhibition by lapatinib. [J]. Cancer research: The official organ of the American Association for Cancer Research, Inc 2008, 2(2).
[8] Levitzki A, Gazit A. TYROSINE KINASE INHIBITION - AN APPROACH TO DRUG DEVELOPMENT [Review] [J]. Science 1995, 5205(5205).
[9] Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. [J]. The New England journal of medicine 2002, 2(2).
[10] Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. [J]. The New England journal of medicine 2006, 6(6).
[11] MARJOU A D, THIERY J P, RADVANYI E. Involvement of epidermal growth factor receptor in chemically induced mouse bladder tumor progression [J]. Carcinogenesis 2000, 21(12).
[12] BREHMER D, GREFF Z, GODL K. Cellular targets of gefitinib [J]. Cancer Research 2005, 65(02).
[13] 章砚东. 喹唑啉类化合物库的固相合成, 生物活性筛选及钐式剂在有机合成中的应用 [D]. 杭州:浙江大学 2007.
[14] Dillon RL, White DE, Muller WJ. The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer. [J]. Oncogene 2007, 9(9).
