Trapoxin A Analogue as a Selective Nanomolar Inhibitor of HDAC11.
Trapoxin A Analogue as a Selective Nanomolar Inhibitor of HDAC11.
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DOI：
10.1021/acschembio.2c00840
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发表时间：
2023-04-21
影响因子：
4
通讯作者：
Lin, Hening
中科院分区：
文献类型：
--
作者：
Ho, Thanh Tu;Peng, Changmin;Seto, Edward;Lin, Hening
Histone deacetylases (HDACs) are enzymes that regulate many important biological pathways. There is a need for the development of isoform-selective HDAC inhibitors for further biological applications. Here, we report the development of trapoxin A analogues as potent and selective inhibitors of HDAC11, an enzyme that can efficiently remove long-chain fatty acyl groups from proteins. In particular, we show that one of the trapoxin A analogues, TD034, has nanomolar potency in enzymatic assays. We show that in cells, TD034 is active at low micromolar concentrations and inhibits the defatty acylation of SHMT2, a known HDAC11 substrate. The high potency and selectivity of TD034 would permit further development of HDAC11 inhibitors for biological and therapeutic applications.
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