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HDAC 抑制剂的发现与开发:治疗癌症的方法——综述。

Discovery and Development of HDAC Inhibitors: Approaches for the Treatment of Cancer a Mini-review.

机构信息

Department of Pharmaceutical Chemistry, R K University, Rajkot, 360020, Gujarat, India.

Department of Pharmaceutical Chemistry, School of Pharmacy, R K University, Rajkot, 360020, Gujarat, India.

出版信息

Curr Drug Discov Technol. 2024;21(6):e230224227378. doi: 10.2174/0115701638286941240217102948.

Abstract

Histone deacetylase (HDAC) inhibitors have emerged as promising cancer therapeutics due to their ability to induce differentiation, cell cycle arrest, and apoptosis in cancer cells. In the present review, we have described the systemic discovery and development of HDAC inhibitors. Researchers across the globe have identified various small molecules like benzo[d][1,3]dioxol derivatives, belinostat analogs, pyrazine derivatives, quinazolin-4-one-based derivatives, 2,4-imidazolinedione derivatives, acridine hydroxamic acid derivatives, coumarin derivatives, tetrahydroisoquinoline derivatives, thiazole-5-carboxamide, salicylamide derivatives, β-peptoid-capped HDAC inhibitors, quinazoline derivatives, benzimidazole and benzothiazole derivatives, and β- elemene scaffold containing HDAC inhibitors. Most of the scaffolds have shown attractive IC50 (μM) in various cell lines like HDAC1, HDAC2, HDAC6, PI3K, HeLa, MDA-MB-231, MCF-10A, MCF-7, U937, K562 and Bcr-Abl cell lines.

摘要

组蛋白去乙酰化酶(HDAC)抑制剂由于能够诱导癌细胞分化、细胞周期停滞和凋亡,因此成为有前途的癌症治疗药物。在本综述中,我们描述了 HDAC 抑制剂的系统发现和开发。全球的研究人员已经确定了各种小分子,如苯并[d][1,3]二恶唑衍生物、贝林司他类似物、哒嗪衍生物、喹唑啉-4-酮衍生物、2,4-咪唑啉二酮衍生物、吖啶羟肟酸衍生物、香豆素衍生物、四氢异喹啉衍生物、噻唑-5-甲酰胺、水杨酰胺衍生物、β-肽拟似物封端的 HDAC 抑制剂、喹唑啉衍生物、苯并咪唑和苯并噻唑衍生物,以及含有β-榄香烯支架的 HDAC 抑制剂。大多数支架在各种细胞系(如 HDAC1、HDAC2、HDAC6、PI3K、HeLa、MDA-MB-231、MCF-10A、MCF-7、U937、K562 和 Bcr-Abl 细胞系)中均显示出有吸引力的 IC50(μM)。

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