Ling Li
Novartis
16 Papers
52 Citations
Ling Li is an academic researcher from Novartis. The author has contributed to research in topics: EZH2 & Histone H3. The author has an hindex of 9, co-authored 15 publications.
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Papers
Histone Methylation by PRC2 Is Inhibited by Active Chromatin Marks
Frank W. Schmitges,Archana B. Prusty,Mahamadou Faty,Alexandra Stützer,Gondichatnahalli M. Lingaraju,Jonathan Aiwazian,Ragna Sack,Daniel Hess,Ling Li,Shaolian Zhou,Richard D. Bunker,Urs Wirth,Tewis Bouwmeester,Andreas Bauer,Nga Ly-Hartig,Kehao Zhao,Ho Man Chan,Justin Gu,Heinz Gut,Wolfgang Fischle,Jürg Müller,Nicolas H. Thomä +21 more
TL;DR: It is found that H3K4me3 inhibits PRC2 activity in an allosteric fashion assisted by the Su(z)12 C terminus, which provides the molecular basis of histone H3 N terminus recognition by thePRC2 Nurf55-Su( z)12 submodule.
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Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation
Wei Qi,Ho Man Chan,Lin Teng,Ling Li,Shannon Chuai,Ruipeng Zhang,Jue Zeng,Min Li,Hong Fan,Ying Lin,Justin Gu,Ophelia Ardayfio,Ji-Hu Zhang,Xiaoxia Yan,Jialuo Fang,Yuan Mi,Man Zhang,Tao Zhou,Grace Feng,Zijun Chen,Guobin Li,Teddy T.C. Yang,Kehao Zhao,Xianghui Liu,Zhengtian Yu,Chris Lu,Peter Atadja,En Li +27 more
TL;DR: A potent and selective small molecule inhibitor, EI1, is developed, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine, providing strong validation of EzH2 as a potential therapeutic target for the treatment of cancer.
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An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED
Wei Qi,Kehao Zhao,Justin Gu,Ying Huang,Youzhen Wang,Hailong Zhang,Man Zhang,Jeff Zhang,Zhengtian Yu,Ling Li,Lin Teng,Shannon Chuai,Chao Zhang,Mengxi Zhao,Ho Man Chan,Zijun Chen,Douglas Fang,Qi Fei,Leying Feng,Lijian Feng,Yuan Gao,Hui Ge,Xinjian Ge,Guobin Li,Andreas Lingel,Ying Lin,Yueqin Liu,Fangjun Luo,Minlong Shi,Long Wang,Zhaofu Wang,Yanyan Yu,Jue Zeng,Chenhui Zeng,Lijun Zhang,Qiong Zhang,Shaolian Zhou,Counde Oyang,Peter Atadja,En Li +39 more
TL;DR: EED226 is reported, a potent and selective PRC2 inhibitor that directly binds to the H3K27me3 binding pocket of EED, and shows similar activity to SAM-competitive inhibitors in blocking H 3K27 methylation ofPRC2 target genes and inducing regression of human lymphoma xenograft tumors.
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Structure-Guided Design of EED Binders Allosterically Inhibiting the Epigenetic Polycomb Repressive Complex 2 (PRC2) Methyltransferase
Andreas Lingel,Martin Sendzik,Ying Huang,Michael Shultz,John Cantwell,Michael Patrick Dillon,Xingnian Fu,John Fuller,Tobias Gabriel,Justin Gu,Xiangqing Jiang,Ling Li,Fang Liang,Maureen Mckenna,Wei Qi,Weijun Rao,Xijun Sheng,Wei Shu,James Sutton,Benjamin R. Taft,Long Wang,Jue Zeng,Hailong Zhang,Maya Zhang,Kehao Zhao,Mika Lindvall,Dirksen E. Bussiere +26 more
TL;DR: The optimization of a chemical series representing a new class of PRC2 inhibitors which acts allosterically via the trimethyllysine pocket of the noncatalytic EED subunit is described.
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Discovery of the Clinical Candidate MAK683: An EED-Directed, Allosteric, and Selective PRC2 Inhibitor for the Treatment of Advanced Malignancies.
Ying Huang,Martin Sendzik,Jeff Zhang,Zhenting Gao,Yongfeng Sun,Long Wang,Justin Gu,Kehao Zhao,Zhengtian Yu,Lijun Zhang,Qiong Zhang,Joachim Blanz,Zijun Chen,Valerie Dubost,Douglas D. Fang,Li-Shi Feng,Xingnian Fu,Michael Kiffe,Ling Li,Fang Luo,Xiao Luo,Yuan Mi,Prakash Mistry,David Pearson,Alessandro Piaia,Clemens Scheufler,Rémi Terranova,Andreas Weiss,Jue Zeng,Hailong Zhang,Mengxi Zhao,Michael Patrick Dillon,Sébastien Jeay,Wei Qi,Jonathan G. Moggs,Carole Pissot-Soldermann,En Li,Peter Atadja,Andreas Lingel,Counde Oyang +39 more
TL;DR: The stepwise optimization of the tool compound EED226 toward the potent and selective EED inhibitor MAK683 (compound 22) and its subsequent preclinical characterization are reported, based on a balanced PK/PD profile, efficacy, and mitigated risk of forming reactive metabolites, which has been selected for clinical development.
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