D
Dirk A. Heerding
Researcher at GlaxoSmithKline
Publications - 53
Citations - 2611
Dirk A. Heerding is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: Protein kinase B & Phosphorylation. The author has an hindex of 20, co-authored 49 publications receiving 2264 citations. Previous affiliations of Dirk A. Heerding include Nycomed.
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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
Characterization of an Akt Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity
Nelson Rhodes,Dirk A. Heerding,Derek R. Duckett,Derek J. Eberwein,Victoria B. Knick,Timothy J. Lansing,Randy T. McConnell,Tona M. Gilmer,Shu-Yun Zhang,Kimberly Robell,Jason A. Kahana,Robert S. Geske,Elena Kleymenova,Anthony E. Choudhry,Zhihong Lai,Jack D. Leber,Elisabeth A. Minthorn,Susan L. Strum,Edgar R. Wood,Pearl S. Huang,Robert A. Copeland,Rakesh Kumar +21 more
TL;DR: In immune-compromised mice implanted with human BT474 breast carcinoma xenografts, a single i.p. administration of GSK690693 inhibited GSK3 beta phosphorylation in a dose- and time-dependent manner and showed reductions in phosphorylated Akt substrates in vivo.
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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.
Journal ArticleDOI
Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction
Aidan G. Gilmartin,Faitg Thomas H,Mark Richter,Arthur Groy,Mark A. Seefeld,Michael G. Darcy,Peng Xin,Kelly Federowicz,Jingsong Yang,Shu-Yun Zhang,Elisabeth A. Minthorn,Jon-Paul Jaworski,Michael D. Schaber,Stan F. Martens,Dean E. McNulty,Robert H. Sinnamon,Hong Zhang,Robert B. Kirkpatrick,Neysa Nevins,Guanglei Cui,Beth Pietrak,Elsie Diaz,Amber D. Jones,Martin Brandt,Benjamin Schwartz,Dirk A. Heerding,Rakesh Kumar +26 more
TL;DR: GSK2830371 is the first orally active, allosteric inhibitor of Wip1 phosphatase, an oncogenic phosphat enzyme common to multiple cancers and results in expected pharmacodynamic effects and causes inhibition of lymphoma xenograft growth.
Journal ArticleDOI
Discovery of a Novel and Potent Class of FabI-Directed Antibacterial Agents
David J. Payne,William H. Miller,Valerie Berry,John Brosky,Walter J. Burgess,Emile Chen,Walter E. DeWolf,Andrew P. Fosberry,Rebecca Claire Greenwood,Martha S. Head,Dirk A. Heerding,Cheryl A. Janson,Deborah Dee Jaworski,Paul M. Keller,Manley Peter J,Terrance D. Moore,Kenneth A. Newlander,Stewart C. Pearson,Brian J. Polizzi,Xiayang Qiu,Stephen Rittenhouse,Courtney Slater-Radosti,Kevin L. Salyers,Mark A. Seefeld,Martin G. Smyth,Dennis T. Takata,Irene N. Uzinskas,Kalindi Vaidya,Nicola G. Wallis,Scott B. Winram,Catherine C.K. Yuan,William F. Huffman +31 more
TL;DR: Results show that compound 4 is representative of a new, totally synthetic series of antibacterial agents that has the potential to provide novel alternatives for the treatment of S. aureus infections that are resistant to the present armory of antibiotics.