SIRT1 and SIRT2 inhibitors(University of Kuopio)(SIRT1 and SIRT2 inhibitors(University of Kuopio))

概要

基本信息

药物类型

小分子化药

别名-

靶点

SIRT1 x SIRT2

作用机制

SIRT1抑制剂(NAD依赖性脱乙酰酶sirtuin-1抑制剂)、SIRT2抑制剂(sirtuin 2 inhibitors)

治疗领域-

在研适应症-

非在研适应症-

原研机构

University of Kuopio

在研机构

University of Kuopio

非在研机构-

最高研发阶段药物发现

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 SIRT1 and SIRT2 inhibitors(University of Kuopio) 相关的临床结果

登录后查看更多信息

100 项与 SIRT1 and SIRT2 inhibitors(University of Kuopio) 相关的转化医学

登录后查看更多信息

100 项与 SIRT1 and SIRT2 inhibitors(University of Kuopio) 相关的专利（医药）

登录后查看更多信息

1

项与 SIRT1 and SIRT2 inhibitors(University of Kuopio) 相关的文献（医药）

PLOS ONE

A homogeneous time-resolved fluorescence screen to identify SIRT2 deacetylase and defatty-acylase inhibitors

Article

作者: Weiser, Brian P ; Cassel, Joel ; Yang, Jie ; Ahn, Young-Hoon ; Boyle, Brian C ; Oppong, Daniel

Human sirtuin-2 (SIRT2) has emerged as an attractive drug target for a variety of diseases. The enzyme is a deacylase that can remove chemically different acyl modifications from protein lysine residues. Here, we developed a high-throughput screen based on a homogeneous time-resolved fluorescence (HTRF) binding assay to identify inhibitors of SIRT2’s demyristoylase activity, which is uncommon among many ligands that only affect its deacetylase activity. From a test screen of 9600 compounds, we identified a small molecule that inhibited SIRT2’s deacetylase activity (IC50 = 7 μM) as well as its demyristoylase activity (IC50 = 37 μM). The inhibitor was composed of two small fragments that independently inhibited SIRT2: a halogenated phenol fragment inhibited its deacetylase activity, and a tricyclic thiazolobenzimidazole fragment inhibited its demyristoylase activity. The high-throughput screen also detected multiple deacetylase-specific SIRT2 inhibitors.

100 项与 SIRT1 and SIRT2 inhibitors(University of Kuopio) 相关的药物交易

登录后查看更多信息