1450662-05-1Relevant articles and documents
Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents
Zhou, Qifan,Jia, Lina,Du, Fangyu,Dong, Xiaoyu,Sun, Wanyu,Wang, Lihui,Chen, Guoliang
supporting information, p. 2247 - 2255 (2020/02/20)
Zeste enhancer homolog 2 (EZH2) is highly expressed in various malignant tumors, which could silence tumor suppressor genes via trimethylation of H3K27. Herein was first reported a novel series of pyrrole-3-carboxamide derivatives carrying a pyridone fragment as EZH2 inhibitors. By combining computational modeling, in vitro cellular assays and further rational structure-activity relationship exploration and optimization, compound DM-01 showed powerful inhibition towards EZH2. DM-01 was found to have significant ability to reduce the cellular H3K27me3 level in K562 cells in the Western blot test. Meanwhile, our data showed that knockdown EZH2 in A549 cells resulted in a decrease of cell sensitivity to DM-01 at 50 and 100 μM. DM-01 could also increase the transcription expression of DIRAS3 in a dose-dependent manner, a tumor suppressor in the downstream of EZH2, suggesting it was worth investigating further as a lead compound.
Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitabl
Vaswani, Rishi G.,Gehling, Victor S.,Dakin, Les A.,Cook, Andrew S.,Nasveschuk, Christopher G.,Duplessis, Martin,Iyer, Priyadarshini,Balasubramanian, Srividya,Zhao, Feng,Good, Andrew C.,Campbell, Robert,Lee, Christina,Cantone, Nico,Cummings, Richard T.,Normant, Emmanuel,Bellon, Steven F.,Albrecht, Brian K.,Harmange, Jean-Christophe,Trojer, Patrick,Audia, James E.,Zhang, Ying,Justin, Neil,Chen, Shuyang,Wilson, Jon R.,Gamblin, Steven J.
supporting information, p. 9928 - 9941 (2016/11/19)
Polycomb repressive complex 2 (PRC2) has been shown to play a major role in transcriptional silencing in part by installing methylation marks on lysine 27 of histone 3. Dysregulation of PRC2 function correlates with certain malignancies and poor prognosis
INDOLE DERIVATIVES AS MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Paragraph 00154; 00158, (2015/02/25)
Agents of formulas (l)/(ll)/(lll) for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.