Sirtuin modulators: where are we now? A review of patents from 2015 to 2019

被引:49
作者
Mautone, Nicola [1 ]
Zwergel, Clemens [1 ,2 ]
Mai, Antonello [1 ]
Rotili, Dante [1 ]
机构
[1] Sapienza Univ Roma, Dipartimento Chim & Tecnol Farmaco, Ple A Moro 5, I-00185 Rome, Italy
[2] Univ Campania, Dipartimento Med Precis Luigi Vanvitell, Naples, Italy
关键词
Epigenetics; sirtuins; aging; cancer; neurodegeneration; small molecule modulators; HISTONE DEACETYLASE SIRT1; SMALL-MOLECULE ACTIVATORS; TUMOR-SUPPRESSOR; SELECTIVE INHIBITORS; CALORIE RESTRICTION; CRYSTAL-STRUCTURES; GENE-EXPRESSION; CELL-SURVIVAL; CANCER-CELLS; DISCOVERY;
D O I
10.1080/13543776.2020.1749264
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In recent years, sirtuins (SIRTs) gained an increasing consideration because of their multiple key roles in several biological settings such as the regulation of transcription, energetic metabolism, cell cycle progression, and cytodifferentiation, apoptosis, neuro- and cardio-protection, inflammation, cancer onset and progression. Since there is mounting evidence in favor of potential therapeutic applications of SIRT modulators in various age-related disorders, the search about them is quite active. Areas covered: This review includes the patents regarding SIRT modulators released from 2015 to 2019 and provides an overview of the most relevant SIRT modulators. Expert opinion: Despite the knowledge about this family of broad-spectrum protein lysine deacylases has recently massively increased, there are still open questions, first of all, the exact nature of their involvement in various age-related conditions. The search for isoform-specific SIRT activators and inhibitors is still at its infancy, a limited number of patents describing them has been released, and not many clinical trials are ongoing. However, it is extremely likely that the successes obtained in the structural elucidation and structure-based design approaches that very recently have led to potent and specific SIRT modulators will pave the way for the development of further compounds selective for every single isoform.
引用
收藏
页码:389 / 407
页数:19
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