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Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy.
Huang Y, Zhang J, Yu Z, Zhang H, Wang Y, Lingel A, Qi W, Gu J, Zhao K, Shultz MD, Wang L, Fu X, Sun Y, Zhang Q, Jiang X, Zhang J, Zhang C, Li L, Zeng J, Feng L, Zhang C, Liu Y, Zhang M, Zhang L, Zhao M, Gao Z, Liu X, Fang D, Guo H, Mi Y, Gabriel T, Dillon MP, Atadja P, Oyang C. Huang Y, et al. Among authors: zhang l, zhang m, zhang c, zhang q, zhang j, zhang h. J Med Chem. 2017 Mar 23;60(6):2215-2226. doi: 10.1021/acs.jmedchem.6b01576. Epub 2017 Feb 6. J Med Chem. 2017. PMID: 28092155
Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease.
Jiang Y, Andrews SW, Condroski KR, Buckman B, Serebryany V, Wenglowsky S, Kennedy AL, Madduru MR, Wang B, Lyon M, Doherty GA, Woodard BT, Lemieux C, Geck Do M, Zhang H, Ballard J, Vigers G, Brandhuber BJ, Stengel P, Josey JA, Beigelman L, Blatt L, Seiwert SD. Jiang Y, et al. Among authors: zhang h. J Med Chem. 2014 Mar 13;57(5):1753-69. doi: 10.1021/jm400164c. Epub 2013 May 28. J Med Chem. 2014. PMID: 23672640
NSD2 is recruited through its PHD domain to oncogenic gene loci to drive multiple myeloma.
Huang Z, Wu H, Chuai S, Xu F, Yan F, Englund N, Wang Z, Zhang H, Fang M, Wang Y, Gu J, Zhang M, Yang T, Zhao K, Yu Y, Dai J, Yi W, Zhou S, Li Q, Wu J, Liu J, Wu X, Chan H, Lu C, Atadja P, Li E, Wang Y, Hu M. Huang Z, et al. Among authors: zhang m, zhang h. Cancer Res. 2013 Oct 15;73(20):6277-88. doi: 10.1158/0008-5472.CAN-13-1000. Epub 2013 Aug 26. Cancer Res. 2013. PMID: 23980095
Structure-Guided Design of EED Binders Allosterically Inhibiting the Epigenetic Polycomb Repressive Complex 2 (PRC2) Methyltransferase.
Lingel A, Sendzik M, Huang Y, Shultz MD, Cantwell J, Dillon MP, Fu X, Fuller J, Gabriel T, Gu J, Jiang X, Li L, Liang F, McKenna M, Qi W, Rao W, Sheng X, Shu W, Sutton J, Taft B, Wang L, Zeng J, Zhang H, Zhang M, Zhao K, Lindvall M, Bussiere DE. Lingel A, et al. Among authors: zhang m, zhang h. J Med Chem. 2017 Jan 12;60(1):415-427. doi: 10.1021/acs.jmedchem.6b01473. Epub 2017 Jan 3. J Med Chem. 2017. PMID: 27992714
Discovery and Molecular Basis of a Diverse Set of Polycomb Repressive Complex 2 Inhibitors Recognition by EED.
Li L, Zhang H, Zhang M, Zhao M, Feng L, Luo X, Gao Z, Huang Y, Ardayfio O, Zhang JH, Lin Y, Fan H, Mi Y, Li G, Liu L, Feng L, Luo F, Teng L, Qi W, Ottl J, Lingel A, Bussiere DE, Yu Z, Atadja P, Lu C, Li E, Gu J, Zhao K. Li L, et al. Among authors: zhang m, zhang jh, zhang h. PLoS One. 2017 Jan 10;12(1):e0169855. doi: 10.1371/journal.pone.0169855. eCollection 2017. PLoS One. 2017. PMID: 28072869 Free PMC article.
An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED.
Qi W, Zhao K, Gu J, Huang Y, Wang Y, Zhang H, Zhang M, Zhang J, Yu Z, Li L, Teng L, Chuai S, Zhang C, Zhao M, Chan H, Chen Z, Fang D, Fei Q, Feng L, Feng L, Gao Y, Ge H, Ge X, Li G, Lingel A, Lin Y, Liu Y, Luo F, Shi M, Wang L, Wang Z, Yu Y, Zeng J, Zeng C, Zhang L, Zhang Q, Zhou S, Oyang C, Atadja P, Li E. Qi W, et al. Among authors: zhang l, zhang m, zhang c, zhang q, zhang j, zhang h. Nat Chem Biol. 2017 Apr;13(4):381-388. doi: 10.1038/nchembio.2304. Epub 2017 Jan 30. Nat Chem Biol. 2017. PMID: 28135235
Discovery of Small-Molecule Antagonists of the H3K9me3 Binding to UHRF1 Tandem Tudor Domain.
Senisterra G, Zhu HY, Luo X, Zhang H, Xun G, Lu C, Xiao W, Hajian T, Loppnau P, Chau I, Li F, Allali-Hassani A, Atadja P, Oyang C, Li E, Brown PJ, Arrowsmith CH, Zhao K, Yu Z, Vedadi M. Senisterra G, et al. Among authors: zhang h. SLAS Discov. 2018 Oct;23(9):930-940. doi: 10.1177/2472555218766278. Epub 2018 Mar 21. SLAS Discov. 2018. PMID: 29562800 Free article.
Discovery of the Clinical Candidate MAK683: An EED-Directed, Allosteric, and Selective PRC2 Inhibitor for the Treatment of Advanced Malignancies.
Huang Y, Sendzik M, Zhang J, Gao Z, Sun Y, Wang L, Gu J, Zhao K, Yu Z, Zhang L, Zhang Q, Blanz J, Chen Z, Dubost V, Fang D, Feng L, Fu X, Kiffe M, Li L, Luo F, Luo X, Mi Y, Mistry P, Pearson D, Piaia A, Scheufler C, Terranova R, Weiss A, Zeng J, Zhang H, Zhang J, Zhao M, Dillon MP, Jeay S, Qi W, Moggs J, Pissot-Soldermann C, Li E, Atadja P, Lingel A, Oyang C. Huang Y, et al. Among authors: zhang l, zhang q, zhang j, zhang h. J Med Chem. 2022 Apr 14;65(7):5317-5333. doi: 10.1021/acs.jmedchem.1c02148. Epub 2022 Mar 30. J Med Chem. 2022. PMID: 35352560
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