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用于三阴性乳腺癌治疗的组蛋白去乙酰化酶抑制剂

HDAC Inhibitors for the Therapy of Triple Negative Breast Cancer.

作者信息

Maccallini Cristina, Ammazzalorso Alessandra, De Filippis Barbara, Fantacuzzi Marialuigia, Giampietro Letizia, Amoroso Rosa

机构信息

Department of Pharmacy, University G. d'Annunzio of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy.

出版信息

Pharmaceuticals (Basel). 2022 May 26;15(6):667. doi: 10.3390/ph15060667.

Abstract

Triple negative breast cancer (TNBC) is an urgent as well as huge medical challenge, which is associated with poor prognosis and responsiveness to chemotherapies. Since epigenetic changes are highly implicated in TNBC tumorigenesis and development, inhibitors of histone deacetylases (HDACIs) could represent a promising therapeutic strategy. Although clinical trials involving single HDACIs showed disappointing results against TNBC, recent studies emphasize the high potential impact of HDACIs in controlling TNBC. In addition, encouraging results stem from new compounds designed to obtain isoform selectivity and/or polypharmacological HDAC approach. The present review provides a discussion of the HDACIs pharmacophoric models and of the structural modifications, leading to compounds with a potent activity against TNBC progression.

摘要

三阴性乳腺癌(TNBC)是一项紧迫且巨大的医学挑战,它与预后不良以及对化疗的反应性有关。由于表观遗传变化在TNBC的肿瘤发生和发展中高度相关,组蛋白去乙酰化酶抑制剂(HDACIs)可能代表一种有前景的治疗策略。尽管涉及单一HDACIs的临床试验针对TNBC显示出令人失望的结果,但最近的研究强调了HDACIs在控制TNBC方面的高潜在影响。此外,设计用于获得亚型选择性和/或多药理学HDAC方法的新化合物产生了令人鼓舞的结果。本综述讨论了HDACIs的药效团模型以及结构修饰,这些修饰导致了对TNBC进展具有强效活性的化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/280a/9230362/d3b48b113132/pharmaceuticals-15-00667-g001.jpg

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