1173081-96-3Relevant articles and documents
Identification of potent, selective, cell-Active inhibitors of the histone lysine methyltransferase EZH2
Verma, Sharad K.,Tian, Xinrong,Lafrance, Louis V.,Duquenne, Céline,Suarez, Dominic P.,Newlander, Kenneth A.,Romeril, Stuart P.,Burgess, Joelle L.,Grant, Seth W.,Brackley, James A.,Graves, Alan P.,Scherzer, Daryl A.,Shu, Art,Thompson, Christine,Ott, Heidi M.,Van Aller, Glenn S.,MacHutta, Carl A.,Diaz, Elsie,Jiang, Yong,Johnson, Neil W.,Knight, Steven D.,Kruger, Ryan G.,McCabe, Michael T.,Dhanak, Dashyant,Tummino, Peter J.,Creasy, Caretha L.,Miller, William H.
, p. 1091 - 1096 (2012)
The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-Active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.
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.
EZH2 inhibitor as well as preparation of EZH2 inhibitor and application of EZH2 inhibitor in anti-tumor treatment
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Paragraph 0104-0106, (2019/08/20)
The invention discloses an EZH2 inhibitor as well as preparation of the EZH2 inhibitor and application of the EZH2 inhibitor in anti-tumor treatment. The EZH2 inhibitor has a structure represented bya general formula I shown in the description, wherein de