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William J. Zavadoski
Researcher at Pfizer
Publications - 18
Citations - 894
William J. Zavadoski is an academic researcher from Pfizer. The author has contributed to research in topics: In vivo & Insulin. The author has an hindex of 13, co-authored 18 publications receiving 803 citations.
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Journal ArticleDOI
Acute Effects of Atypical Antipsychotics on Whole-Body Insulin Resistance in Rats: Implications for Adverse Metabolic Effects
Karen L. Houseknecht,Alan Robertson,William J. Zavadoski,E. Michael Gibbs,David E. Johnson,Hans Rollema +5 more
TL;DR: OLAN and CLOZ can thus rapidly induce marked insulin resistance, which could contribute to the hyperglycemia and ketoacidosis reported for patients receiving those therapies.
Journal ArticleDOI
Discovery of (S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid as a hepatoselective glucokinase activator clinical candidate for treating type 2 diabetes mellitus.
Jeffrey A. Pfefferkorn,Angel Guzman-Perez,John Litchfield,Robert J. Aiello,Judith L. Treadway,John C. Pettersen,Martha L. Minich,Kevin J. Filipski,Christopher S. Jones,Meihua Tu,Gary Erik Aspnes,Hud Lawrence Risley,Jianwei Bian,Benjamin D. Stevens,Patricia Bourassa,Theresa D’Aquila,Levenia Baker,Nicole Barucci,Alan Robertson,Francis Bourbonais,David R. Derksen,Margit MacDougall,Over Cabrera,Jing Chen,Amanda L. Lapworth,James A. Landro,William J. Zavadoski,Karen Atkinson,Nahor Haddish-Berhane,Beijing Tan,Lili Yao,Rachel E. Kosa,Manthena V.S. Varma,Bo Feng,David B. Duignan,Ayman El-Kattan,Sharad B. Murdande,Shenping Liu,Mark Ammirati,John D. Knafels,Paul DaSilva-Jardine,Laurel Sweet,Spiros Liras,Timothy P. Rolph +43 more
TL;DR: 19 is identified as a potent glucokinase activator with a greater than 50-fold liver-to-pancreas ratio of tissue distribution in rodent and non-rodent species, leading to its selection as a clinical development candidate for treating type 2 diabetes.
Journal ArticleDOI
Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1
Robert L. Dow,Jian-Cheng Li,Michael Patrick Pence,E. Michael Gibbs,Jennifer L. LaPerle,John Litchfield,David W. Piotrowski,Michael John Munchhof,Tara B. Manion,William J. Zavadoski,Gregory S. Walker,R. Kirk McPherson,Susan Tapley,Eliot Sugarman,Angel Guzman-Perez,Paul DaSilva-Jardine +15 more
TL;DR: Compound 3 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity versus a broad panel of off-target pharmacologic end points and has been advanced to human clinical studies.
Journal ArticleDOI
A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.
Sumeet A. Khetarpal,Xuemei Zeng,John S. Millar,Cecilia Vitali,Amritha Varshini Hanasoge Somasundara,Paolo Zanoni,James A. Landro,Nicole Barucci,William J. Zavadoski,Zhiyuan Sun,Hans De Haard,Ildiko Toth,Gina M. Peloso,Pradeep Natarajan,Pradeep Natarajan,Marina Cuchel,Sissel Lund-Katz,Michael C. Phillips,Alan R. Tall,Sekar Kathiresan,Sekar Kathiresan,Paul DaSilva-Jardine,Nathan A. Yates,Daniel J. Rader +23 more
TL;DR: A monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apo C-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo is developed.
Journal ArticleDOI
Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR) knockout mice: implications on anti-glucagon therapies for diabetes
Jianxin Yang,Margit MacDougall,Michael T. McDowell,Li Xi,Ru Wei,William J. Zavadoski,Mark P. Molloy,John D Baker,John D Baker,Max Kuhn,Over Cabrera,Judith L. Treadway +11 more
TL;DR: The results of this study suggest that the complete ablation of hepatic glucagon receptor function results in major metabolic alterations in the liver, which, while promoting improved glycemic control, may be associated with adverse lipid changes.