دورية أكاديمية
Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2.
| العنوان: | Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. |
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| المؤلفون: | Verma SK; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Tian X; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., LaFrance LV; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Duquenne C; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Suarez DP; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Newlander KA; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Romeril SP; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Burgess JL; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Grant SW; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Brackley JA; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Graves AP; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Scherzer DA; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Shu A; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Thompson C; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Ott HM; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Aller GS; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Machutta CA; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Diaz E; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Jiang Y; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Johnson NW; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Knight SD; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Kruger RG; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., McCabe MT; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Dhanak D; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Tummino PJ; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Creasy CL; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States., Miller WH; Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States. |
| المصدر: | ACS medicinal chemistry letters [ACS Med Chem Lett] 2012 Oct 19; Vol. 3 (12), pp. 1091-6. Date of Electronic Publication: 2012 Oct 19 (Print Publication: 2012). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101521073 Publication Model: eCollection Cited Medium: Print ISSN: 1948-5875 (Print) Linking ISSN: 19485875 NLM ISO Abbreviation: ACS Med Chem Lett Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Chemical Society |
| مستخلص: | 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. |
| References: | Nature. 2012 Dec 6;492(7427):108-12. (PMID: 23051747) Bioorg Med Chem Lett. 2009 Feb 15;19(4):1218-23. (PMID: 19131248) J Biomol Screen. 2012 Dec;17(10):1279-92. (PMID: 22904200) Mutat Res. 2008 Dec 1;647(1-2):21-9. (PMID: 18723033) J Med Chem. 2009 Dec 24;52(24):7950-3. (PMID: 19891491) Nat Rev Immunol. 2009 Feb;9(2):91-105. (PMID: 19151746) J Med Chem. 2010 Aug 12;53(15):5844-57. (PMID: 20614940) Cancer Sci. 2011 Jul;102(7):1298-305. (PMID: 21539681) Nat Genet. 2010 Feb;42(2):181-5. (PMID: 20081860) Nat Genet. 2010 Aug;42(8):722-6. (PMID: 20601953) Structure. 2011 Sep 7;19(9):1262-73. (PMID: 21782458) Cell. 2007 Feb 23;128(4):693-705. (PMID: 17320507) PLoS One. 2010 Jan 11;5(1):e8570. (PMID: 20084102) Cancer Cell. 2011 Jul 12;20(1):53-65. (PMID: 21741596) Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11606-11. (PMID: 14500907) Nature. 2011 Jul 27;476(7360):298-303. (PMID: 21796119) BMC Cancer. 2010 Oct 04;10:524. (PMID: 20920340) J Am Chem Soc. 2011 Oct 26;133(42):16746-9. (PMID: 21936531) Nat Chem Biol. 2012 Nov;8(11):890-6. (PMID: 23023262) Nature. 2002 Oct 10;419(6907):624-9. (PMID: 12374981) Mol Cancer Ther. 2009 Jun;8(6):1579-88. (PMID: 19509260) Prostate. 2007 Apr 1;67(5):547-56. (PMID: 17252556) Nat Genet. 2011 Jul 31;43(9):830-7. (PMID: 21804550) Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2989-94. (PMID: 22323599) Nat Chem Biol. 2011 Jul 10;7(8):566-74. (PMID: 21743462) Cell. 2007 Feb 23;128(4):683-92. (PMID: 17320506) Nat Rev Neurosci. 2007 May;8(5):355-67. (PMID: 17453016) Oncogene. 2009 Feb 12;28(6):843-53. (PMID: 19079346) Br J Cancer. 2012 Jan 17;106(2):243-7. (PMID: 22187039) |
| فهرسة مساهمة: | Keywords: EZH2; Epigenetics; H3K27me3; PRC2; SAM-competitive inhibitor; methyltransferase |
| تواريخ الأحداث: | Date Created: 20140606 Date Completed: 20140605 Latest Revision: 20220330 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC4025676 |
| DOI: | 10.1021/ml3003346 |
| PMID: | 24900432 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1948-5875 |
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| DOI: | 10.1021/ml3003346 |