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Hedgehog信号通道广泛地存在于人的体内,它主要参与了胚胎的发育与形成。在成年人体内,除了参与机体组织的维持以及修复外Hedgehog信号通道总是处于抑制状态。当它异常激活时会形成一系列的疾病,例如基底细胞癌以及髓母细胞瘤、乳腺癌、结肠癌、卵巢癌、前列腺癌等。除了环巴胺及其类似物外,已经发现了一些对Hedgehog信号通道具有抑制作用的小分子化合物,特别是GDC-0449于2012年1月被FDA批准用于治疗基底细胞癌,证明Hedgehog信号通道是可以用于治疗癌症的一个新靶点。本文主要综述了已经报道的对Hedgehog信号通道具有抑制作用且具有代表性的小分子抑制剂的结构以及它们相关的生物数据。
Hedgehog signaling pathway exists widely in the human body, it is mainly involved in the development and formation of embryos. In adults, the Hedgehog signaling pathway is always in an inhibitory state, except for the maintenance and repair of the body’s tissues. When it is abnormally activated, it will form a series of diseases, such as basal cell carcinoma and medulloblastoma, breast cancer, colon cancer, ovarian cancer, prostate cancer and the like. In addition to cyclopamine and its analogues, several small molecule compounds have been found that inhibit the Hedgehog signaling pathway. In particular, GDC-0449 was approved by the FDA in January 2012 for the treatment of basal cell carcinoma, demonstrating that the Hedgehog signaling pathway Is a new target that can be used to treat cancer. This review summarizes the reported structures of small molecule inhibitors that have an inhibitory effect on Hedgehog signaling and their associated biological data.