Autophagic effect of SAM-competitive EZH2 inhibitors on cancer cells
نویسندگان
چکیده
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan Mackay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan Department of Medicine, Mackay Medical College, New Taipei City, Taiwan Liver Medical Center, Mackay Memorial Hospital, Taipei, Taiwan
منابع مشابه
S-Adenosyl-l-methionine-competitive inhibitors of the histone methyltransferase EZH2 induce autophagy and enhance drug sensitivity in cancer cells
The enhancer of zeste homolog 2 (EZH2) has emerged as a novel anticancer target. Various EZH2 inhibitors have been developed in recent years. Among these, 3-deazaneplanocin A (DZNep) is known to deplete EZH2 protein expression through an indirect pathway. In contrast, GSK343 directly inhibits enzyme activity through an S-adenosyl-L-methionine-competitive pathway. Therefore, we proposed that DZN...
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Recently, the epigenetic modifications have been recognized as a regulator of gene expression in various cancers. EZH2 gene is one the most important component of the PRC2 complex. Overexpression of EZH2 was identified in multiple cancers that considered more attractive the EZH2 role as an oncogene. Some studies report that EZH2 contributes to various aspects of colorectal cancer (CRC). However...
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There are currently no effective molecular targeted therapies for hepatocellular carcinoma (HCC), the third leading cause of cancer-related death worldwide. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 (H3K27)-specific methyltransferase, has been emerged as novel anticancer target. Our previous study has demonstrated that GSK343, an S-adenosyl-L-methionine (SAM)-competitive inhibi...
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The identification and development of a novel series of small molecule Enhancer of Zeste Homologue 2 (EZH2) inhibitors is described. A concise and modular synthesis enabled the rapid development of structure-activity relationships, which led to the identification of 44 as a potent, SAM-competitive inhibitor of EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma cells.
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