Maschinot C A, Pace J R, Hadden M K
Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Unit 3092, Storrs, CT 06269-3092, USA.
Curr Med Chem. 2015;22(35):4033-57. doi: 10.2174/0929867322666150827093904.
The hedgehog (Hh) pathway is a developmental signaling pathway that is essential to the proper embryonic development of many vertebrate systems. Dysregulation of Hh signaling has been implicated as a causative factor in the development and progression of several forms of human cancer. As such, the development of small molecule inhibitors of Hh signaling as potential anti-cancer chemotherapeutics has been a major area of research interest in both academics and industry over the past ten years. Through these efforts, synthetic small molecules that target multiple components of the Hh pathway have been identified and advanced to preclinical or clinical development. The goal of this review is to provide an update on the current status of several synthetic small molecule Hh pathway inhibitors and explore the potential of several recently disclosed inhibitory scaffolds.
刺猬信号通路（Hh）是一种发育信号通路，对许多脊椎动物系统的正常胚胎发育至关重要。Hh信号失调被认为是多种人类癌症发生和进展的致病因素。因此，在过去十年中，开发作为潜在抗癌化疗药物的Hh信号小分子抑制剂一直是学术界和工业界研究的主要热点领域。通过这些努力，已经鉴定出靶向Hh通路多个组分的合成小分子，并推进到临床前或临床开发阶段。本综述的目的是提供几种合成小分子Hh通路抑制剂的最新研究进展，并探讨几种最近披露的抑制性骨架的潜力。
