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Alan P. Graves
Researcher at GlaxoSmithKline
Publications - 28
Citations - 3597
Alan P. Graves is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: EZH2 & Histone methyltransferase. The author has an hindex of 16, co-authored 26 publications receiving 3121 citations. Previous affiliations of Alan P. Graves include Research Triangle Park & University of California, San Francisco.
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Journal ArticleDOI
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.
Michael T. McCabe,Heidi M. Ott,Gopinath Ganji,Susan Korenchuk,Christine Thompson,Glenn S. Van Aller,Yan Liu,Alan P. Graves,Anthony Della Pietra,Elsie Diaz,Louis V. LaFrance,Mellinger Mark,Celine Duquenne,Xinrong Tian,Ryan G. Kruger,Charles F. McHugh,Martin Brandt,William H. Miller,Dashyant Dhanak,Sharad K. Verma,Peter J. Tummino,Caretha L. Creasy +21 more
TL;DR: GSK126, a potent, highly selective, S-adenosyl-methionine-competitive, small-molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes and markedly inhibits the growth of EzH2 mutant DLBCL xenografts in mice are demonstrated.
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Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27)
Michael T. McCabe,Alan P. Graves,Gopinath Ganji,Elsie Diaz,Wendy S. Halsey,Yong Jiang,Kimberly N. Smitheman,Heidi M. Ott,Melissa B. Pappalardi,Kimberly E. Allen,Stephanie Chen,Anthony Della Pietra,Edward Dul,Ashley M. Hughes,Seth A. Gilbert,Sara H. Thrall,Peter J. Tummino,Ryan G. Kruger,Martin Brandt,Benjamin J. Schwartz,Caretha L. Creasy +20 more
TL;DR: This mutation highlights the interplay between Y641 and A677 residues in the substrate specificity of EZH2 and identifies another lymphoma patient population that harbors an activating mutation of EzH2.
Journal ArticleDOI
Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2.
Sharad K. Verma,Xinrong Tian,Louis V. LaFrance,Celine Duquenne,Dominic Suarez,Kenneth A. Newlander,Stuart Paul Romeril,Joelle Lorraine Burgess,Seth W. Grant,Brackley James,Alan P. Graves,Daryl A. Scherzer,Art Shu,Christine Thompson,Heidi M. Ott,Glenn S. Van Aller,Carl A. Machutta,Elsie Diaz,Yong Jiang,Johnson Neil W,Steven D. Knight,Ryan G. Kruger,Michael T. McCabe,Dashyant Dhanak,Peter J. Tummino,Caretha L. Creasy,William H. Miller +26 more
TL;DR: This work has identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 and GSK343, which are small molecule chemical tools that would be useful to further explore the biology of EZh2.
Journal ArticleDOI
Predicting absolute ligand binding free energies to a simple model site
David L. Mobley,Alan P. Graves,John D. Chodera,Andrea C. McReynolds,Brian K. Shoichet,Ken A. Dill +5 more
TL;DR: Alchemical free energy calculations in explicit solvent to predict ligand binding in a model cavity in T4 lysozyme are applied, beginning with single poses from docking, then including multiple poses, additional protein conformational changes, and using an improved charge model.
Journal ArticleDOI
Rescoring docking hit lists for model cavity sites: predictions and experimental testing.
Alan P. Graves,Devleena M. Shivakumar,S.E. Boyce,Matthew P. Jacobson,David A. Case,Brian K. Shoichet +5 more
TL;DR: This work re-ranked docking hit lists in three small buried sites in molecular mechanics-generalized Born surface area techniques, and rescoring not only rescued docking false positives, but also introduced several new false positives into the top-ranking molecules.