摘要
在过去的几年里,在肿瘤细胞中识别新的治疗靶点方面的显著进展导致了新的抗肿瘤药物支架的发现和开发。肿瘤细胞表观遗传调控的探索和开发对医药和学术生物医学文献都具有重要意义。表观遗传机制对于组织特异性基因表达的正常发育和维持是必不可少的。破坏表观遗传过程以根除肿瘤细胞是最有前途的癌症控制干预措施之一。Polycomb抑制复合物2(PRC2),一种将组蛋白H3的赖氨酸27甲基化以促进转录沉默的复合物,参与协调细胞中的重要途径。PRC2在许多恶性肿瘤中都被发现过表达,使其成为抗癌治疗的主要靶点。尽管其分子机制很清楚,但其亚基的高激活和耐药突变已成为一个值得讨论的问题。这篇综述概述了目前对PRC2在活性复合物形成中的成分的理解,并评估了它们作为一个有前途的癌症治疗靶点的潜力。我们还回顾了在人类癌症范围内的PRC2成分突变的影响。最后,我们讨论了目前针对PRC2复合物的治疗药物设计的一些挑战。
关键词: 癌症,表观遗传学,PRC2,组蛋白甲基化,药物开发,治疗性。
图形摘要
Current Drug Targets
Title:New Framework for the Discovery of PRC2 Inhibitors: Epigenetic Drugs
Volume: 22 Issue: 11
关键词: 癌症,表观遗传学,PRC2,组蛋白甲基化,药物开发,治疗性。
摘要: Over the past several years, remarkable progress towards the recognition of new therapeutic targets in tumor cells has led to the discovery and development of newer scaffolds of anti-tumor drugs. The exploration and exploitation of epigenetic regulation in tumor cells are of immense importance to both the pharmaceutical and academic biomedical literatures. Epigenetic mechanisms are indispensable for the normal development and maintenance of tissue-specific gene expression. Disruption of epigenetic processes to eradicate tumor cells is among the most promising intervention for cancer control. Polycomb repressive complex 2 (PRC2), a complex that methylates lysine 27 of histone H3 to promote transcriptional silencing, is involved in orchestrating significant pathways in a cell. Overexpression of PRC2 has been found in a number of cancerous malignancies, making it a major target for anti-cancer therapy. Despite its well-understood molecular mechanism, hyperactivation and drug resistance mutations in its subunits have become a matter of discussion. This review outlines the current understanding of the components of PRC2 in active complex formation and assesses their potential as a promising therapeutic target for cancer therapy. We also review the effects of mutations in the PRC2 components, in the purview of human cancers. Finally, we discuss some of the current challenges for therapeutic drug designs targeting the PRC2 complex.
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Cite this article as:
New Framework for the Discovery of PRC2 Inhibitors: Epigenetic Drugs, Current Drug Targets 2021; 22 (11) . https://dx.doi.org/10.2174/1389450122666210215111744
DOI https://dx.doi.org/10.2174/1389450122666210215111744 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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