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首页> 外文期刊>Journal of Pharmacology and Pharmacotherapeutics >The dawn of hedgehog inhibitors: Vismodegib
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The dawn of hedgehog inhibitors: Vismodegib

机译：刺猬抑制剂的诞生：Vismodegib

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Cancer, one of the leading causes of death worldwide is estimated to increase to approximately 13.1 million by 2030. This has amplified the research in oncology towards the exploration of novel targets. Recently there has been lots of interest regarding the hedgehog (Hh) pathway, which plays a significant role in the development of organs and tissues during embryonic and postnatal periods. In a normal person, the Hh signaling pathway is under inhibition and gets activated upon the binding of Hh ligand to a transmembrane receptor called Patched (PTCH1) thus allowing the transmembrane protein, smoothened (SMO) to transfer signals through various proteins. One of the newer drugs namely vismodegib involves the inhibition of Hh pathway and has shown promising results in the treatment of advanced basal-cell carcinoma as well as medulloblastoma. It has been granted approval by US Food and Drug Administration's (US FDA) priority review program on January 30, 2012 for the treatment of advanced basal-cell carcinoma. The drug is also being evaluated in malignancies like medulloblastoma, pancreatic cancer, multiple myeloma, chondrosarcoma and prostate cancer. Moreover various Hh inhibitors namely LDE 225, saridegib, BMS 833923, LEQ 506, PF- 04449913 and TAK-441 are also undergoing phase I and II trials for different neoplasms. Hence this review will describe briefly the Hh pathway and the novel drug vismodegib.Keywords: Advanced basal-cell carcinoma, hedgehog pathway, medulloblastoma
机译：到2030年，癌症是全球主要的死亡原因之一，据估计将增加到约1310万。这扩大了肿瘤学的研究范围，以探索新的靶标。最近，人们对刺猬（Hh）通路产生了浓厚的兴趣，该通路在胚胎和出生后的器官和组织发育中起着重要作用。在正常人中，Hh信号通路受到抑制，并在Hh配体与称为Patched（PTCH1）的跨膜受体结合后被激活，从而使跨膜蛋白变平滑（SMO）通过各种蛋白传递信号。 vismodegib是一种较新的药物，涉及抑制Hh通路，并且在治疗晚期基底细胞癌和髓母细胞瘤方面显示出令人鼓舞的结果。它已于2012年1月30日获得美国食品和药物管理局（US FDA）优先审查计划的批准，用于治疗晚期基底细胞癌。该药物还在髓母细胞瘤，胰腺癌，多发性骨髓瘤，软骨肉瘤和前列腺癌等恶性肿瘤中进行评估。此外，各种Hh抑制剂，即LDE 225，saridegib，BMS 833923，LEQ 506，PF-4449913和TAK-441也正在针对不同的肿瘤进行I和II期试验。因此，本综述将简要描述Hh途径和新型药物vismodegib。关键词：晚期基底细胞癌，刺猬途径，髓母细胞瘤

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