S
Seth W. Grant
Researcher at GlaxoSmithKline
Publications - 10
Citations - 1134
Seth W. Grant is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: Cancer & Kinase. The author has an hindex of 6, co-authored 10 publications receiving 980 citations.
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Journal ArticleDOI
Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK).
Jeffrey M. Axten,Jesus R. Medina,Yanhong Feng,Arthur Shu,Stuart Paul Romeril,Seth W. Grant,William Hoi Hong Li,Dirk A. Heerding,Elisabeth A. Minthorn,Thomas Mencken,Charity Atkins,Qi Liu,Sridhar K. Rabindran,Rakesh Kumar,Xuan Hong,Aaron S. Goetz,Thomas B. Stanley,J. David Taylor,Scott D Sigethy,Ginger H. Tomberlin,Annie M. Hassell,Kirsten M. Kahler,Lisa M. Shewchuk,Robert T. Gampe +23 more
TL;DR: Through screening and lead optimization using the human PERK crystal structure, compound 38 (GSK2606414), an orally available, potent, and selective PERK inhibitor is discovered, which inhibits PERK activation in cells and inhibits the growth of a human tumor xenograft in mice.
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.
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Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical Development
Jeffrey M. Axten,Stuart Paul Romeril,Arthur Shu,Jeffrey M. Ralph,Jesus R. Medina,Yanhong Feng,William Hoi Hong Li,Seth W. Grant,Dirk A. Heerding,Elisabeth A. Minthorn,Thomas Mencken,Nathan Gaul,Aaron S. Goetz,Thomas B. Stanley,A.M. Hassell,Robert T. Gampe,Charity Atkins,Rakesh Kumar +17 more
TL;DR: In continuation of the drug discovery program, a strategy to decrease inhibitor lipophilicity is applied as a means to improve physical properties and pharmacokinetics and is selected for advancement to preclinical development.
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Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors.
Jesus R. Medina,Christopher Becker,Charles W. Blackledge,Celine Duquenne,Yanhong Feng,Seth W. Grant,Dirk A. Heerding,William Hoi Hong Li,William H. Miller,Stuart Paul Romeril,Daryl A. Scherzer,Arthur Shu,Mark A. Bobko,Antony Chadderton,Melissa Dumble,Christine M. Gardiner,Seth A. Gilbert,Qi Liu,Sridhar K. Rabindran,Valery Sudakin,Hong Xiang,Pat Brady,Nino Campobasso,Paris Ward,Jeffrey M. Axten +24 more
TL;DR: The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines, demonstrating the utility of these molecules as tools to further delineate the biology ofPDK1 and the potential pharmacological uses of a PDK 1 inhibitor.
Journal ArticleDOI
Discovery of a new series of Aurora inhibitors through truncation of GSK1070916.
Jesus R. Medina,Seth W. Grant,Jeffrey M. Axten,William H. Miller,Carla A. Donatelli,Mary Ann Hardwicke,Catherine A. Oleykowski,Qiaoyin Liao,Ramona Plant,Hong Xiang +9 more
TL;DR: The SAR results from this investigation will be presented with an emphasis on the impact structural changes have on the cellular phenotype.