Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, Rome, Italy.
Dipartimento di Medicina di Precisione, "Luigi Vanvitelli", Università della Campania, Naples, Italy.
Expert Opin Ther Pat. 2020 Jun;30(6):389-407. doi: 10.1080/13543776.2020.1749264. Epub 2020 Apr 13.
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. : This review includes the patents regarding SIRT modulators released from 2015 to 2019 and provides an overview of the most relevant SIRT modulators.: 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.
近年来,由于其在多个生物学环境中的多种关键作用,如转录调控、能量代谢、细胞周期进展和细胞分化、细胞凋亡、神经和心脏保护、炎症、癌症的发生和进展,沉默调节蛋白(SIRTs)受到了越来越多的关注。由于有越来越多的证据支持 SIRT 调节剂在各种与年龄相关的疾病中的潜在治疗应用,因此对它们的研究非常活跃。本文综述了 2015 年至 2019 年发布的有关 SIRT 调节剂的专利,并对最相关的 SIRT 调节剂进行了概述。尽管最近对这一家族的广谱蛋白质赖氨酸去酰基酶的了解有了大幅增加,但仍存在一些悬而未决的问题,首先是它们在各种与年龄相关的疾病中的确切作用。目前仍处于起步阶段,只有少数专利描述了它们,并且正在进行的临床试验也不多。然而,非常有可能的是,最近在结构阐明和基于结构的设计方法方面取得的成功,这些方法最近导致了高效和特异性的 SIRT 调节剂,将为进一步开发针对每种同工酶的选择性化合物铺平道路。