摘要
背景:维替泊芬是一种卟啉光敏剂用于临床光动力治疗年龄相关性黄斑变性。它几乎同时已被确定为一种YAP/TEAD和自噬抑制剂。在过去的几年中,YAP(TAZ),对小河马途径信号通路的下游效应器,已成为有前途的抗癌靶点,如图所示的实验证据,显示YAP在几种癌症过量。然而,YAP也被发现与细胞自噬、线粒体活性氧/氮物种紧密相连。我们在此回顾最近的研究是用没有激活为YAP / TEAD抑制剂或蛋白寡聚化启动维替泊芬,重点对其的影响而YAP/TEAD靶基因和其他生物标志物与细胞自噬。结果:由于维替泊芬识别为YAP / TEAD抑制剂,在体外和体内研究的几个在不同的癌症发现这个分子的新的潜力,其中YAP过度表达。然而,关于YAP其作用详细的结构信息仍然缺乏。同时,维替泊芬通过促进p62寡聚化被确定为促进自噬抑制剂。此外,维替泊芬是肿瘤选择性毒性(由p62,STAT3齐聚)在结直肠癌。在迄今为止YAP抑制剂唯一生物学特性是作为在细胞和动物模型上使用的至关重要的药物。结论:维替泊芬是一个多靶点药物相互作用与多个蛋白质牵连的主要细胞过程。虽然这并不影响其临床使用,维替泊芬似乎并不是用来药理抑制YAP的理想药物代替。
关键词: 小河马途径信号通路,复杂的YAP/TEAD,非无光诱导治疗,癌基因,细胞自噬,蛋白质毒性
Current Medicinal Chemistry
Title:Non-Photoinduced Biological Properties of Verteporfin
Volume: 23 Issue: 11
Author(s): Floriane Gibault, Matthieu Corvaisier, Fabrice Bailly, Guillemette Huet, Patricia Melnyk, Philippe Cotelle
Affiliation:
关键词: 小河马途径信号通路,复杂的YAP/TEAD,非无光诱导治疗,癌基因,细胞自噬,蛋白质毒性
摘要: Background: Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost simultaneously as a YAP/TEAD and an autophagosome inhibitor. Over the last few years, YAP (TAZ), the downstream effectors of the Hippo pathway, have emerged as promising anticancer targets, as shown by several experimental lines of evidence, showing the overproduction of YAP in several cancers. However, YAP was also found to be closely connected to autophagy, mitochondria and reactive oxygen/nitrogen species. We herein, review the recent studies where VP was used without photoactivation as a YAP/TEAD inhibitor or protein oligomerization promoter, focusing on its effects on the YAP/TEAD gene targets and other biomarkers related to autophagy. Results: Since the identification of VP as YAP/TEAD inhibitor, several in vitro and in vivo studies have revealed the new potential of this molecule in different cancers, where YAP is overexpressed. However, detailed structural information about its interaction with YAP is still lacking. Concomitantly, VP was identified as autophagosome inhibitor by promoting oligomerization of p62. Moreover, VP proves to be tumor-selective proteotoxic (by oligomerization of p62, STAT3) in colorectal cancer. Knowledge on the biological properties of the only YAP inhibitor available to date is vital for its pharmacological use on cellular and animal models. Conclusion: VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD.
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Floriane Gibault, Matthieu Corvaisier, Fabrice Bailly, Guillemette Huet, Patricia Melnyk, Philippe Cotelle , Non-Photoinduced Biological Properties of Verteporfin, Current Medicinal Chemistry 2016; 23 (11) . https://dx.doi.org/10.2174/0929867323666160316125048
DOI https://dx.doi.org/10.2174/0929867323666160316125048 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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