靶向Hedgehog信号通路的抗肿瘤新药研究进展

发布时间：2018-03-22 09:19

本文选题：Hedgehog　切入点：耐药　出处：《药学学报》2017年06期 　论文类型：期刊论文

【摘要】：Hedgehog信号通路在哺乳动物的胚胎发育过程中发挥关键作用,但在成年组织中处于抑制状态。异常激活的Hedgehog信号通路与多种恶性肿瘤的发生发展密切相关,近年来Hedgehog信号通路成为治疗肿瘤的热门靶标。目前已有两种Hedgehog抑制剂(维莫德吉和索尼吉步)上市用于治疗肿瘤,但上市的药物很快出现严重的毒副作用和耐药问题。研究者研发出taladegib、NVP-LEQ506和MRT-92等新型Smo抑制剂以克服维莫德吉的耐药问题,并针对Smo上游Shh配体和下游蛋白Gli蛋白设计相应抑制剂以解决毒副作用问题。同时,目前上市的Hedgehog抑制剂仅用于治疗基底细胞癌,而对其他肿瘤的治疗也在进一步的研究中。现就靶向Hedgehog信号通路的抗肿瘤新药的研发及其治疗不同肿瘤的研究进展进行综述。
[Abstract]:Hedgehog signaling pathway plays a key role in the process of mammalian embryos, but inhibited in adult tissues. Closely related to the occurrence and development of abnormal activation of Hedgehog signaling pathway and a variety of malignant tumors, Hedgehog signaling pathway in recent years become a hot target for the treatment of cancer. There are two kinds of Hedgehog inhibitors (mo de dimension and SONY Kyrgyzstan step) listed for the treatment of tumors, but the drugs listed soon appear side-effects and drug resistance problems. Researchers have developed taladegib, NVP-LEQ506 and MRT-92 and other new Smo inhibitors to overcome drug resistance and dimensional Mo Deji, according to the Smo Shh upstream and downstream protein ligand Gli protein inhibitor designed to solve the side effects the problem. At the same time, the only listed Hedgehog inhibitor for the treatment of basal cell carcinoma, and the treatment of other cancers in further research In this paper, the research and development of new antitumor drugs targeting Hedgehog signaling pathway and the progress in the treatment of different tumors are reviewed.

【作者单位】：上海分子治疗与新药创制工程技术研究中心华东师范大学化学与分子工程学院;
【基金】：国家自然科学基金青年基金资助项目(81402953)
【分类号】：R979.1

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