Hannguang J. Chao
Bristol-Myers Squibb
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Publication
Featured researches published by Hannguang J. Chao.
Journal of Medicinal Chemistry | 2010
Wei Meng; Robert Paul Brigance; Hannguang J. Chao; Aberra Fura; Thomas Harrity; Jovita Marcinkeviciene; Stephen P. O'connor; James Tamura; Dianlin Xie; Yaqun Zhang; Herbert E. Klei; Kevin Kish; Carolyn Weigelt; Huji Turdi; Aiying Wang; Robert Zahler; Mark S. Kirby; Lawrence G. Hamann
Continued structure-activity relationship (SAR) exploration within our previously disclosed azolopyrimidine containing dipeptidyl peptidase-4 (DPP4) inhibitors led us to focus on an imidazolopyrimidine series in particular. Further study revealed that by replacing the aryl substitution on the imidazole ring with a more polar carboxylic ester or amide, these compounds displayed not only increased DPP4 binding activity but also significantly reduced human ether-a-go-go related gene (hERG) and sodium channel inhibitory activities. Additional incremental adjustment of polarity led to permeable molecules which exhibited favorable pharmacokinetic (PK) profiles in preclinical animal species. The active site binding mode of these compounds was determined by X-ray crystallography as exemplified by amide 24c. A subsequent lead molecule from this series, (+)-6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(1-ethyl-1H-pyrazol-5-yl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamide (24s), emerged as a potent, selective DPP4 inhibitor that displayed excellent PK profiles and in vivo efficacy in ob/ob mice.
Journal of Lipid Research | 2015
Joelle M. Onorato; Ching-Hsuen Chu; Zhengping Ma; Lisa M. Kopcho; Hannguang J. Chao; R. Michael Lawrence; Dong Cheng
To demonstrate monoacylglycerol acyltransferase 2 (MGAT2)-mediated enzyme activity in a cellular context, cells of the murine secretin tumor cell-1 line of enteroendocrine origin were used to construct human MGAT2-expressing recombinant cell lines. Low throughput and utilization of radiolabeled substrate in a traditional TLC technique were circumvented by development of a high-resolution LC/MS platform. Monitoring incorporation of stable isotope-labeled D31-palmitate into diacylglycerol (DAG) allowed selective tracing of the cellular DAG synthesis activity. This assay format dramatically reduced background interference and increased the sensitivity and the signal window compared with the TLC method. Using this assay, several MGAT2 inhibitors from different chemotypes were characterized. The described cell-based assay adds a new methodology for the development and evaluation of MGAT2 inhibitors for the treatment of obesity and type 2 diabetes.
Archive | 2005
Hannguang J. Chao; Huji Tuerdi; Timothy Herpin; Jacques Y. Roberge; Yalei Liu; R. Michael Lawrence; Robert Rehfuss; Charles G. Clark; Jennifer X. Qiao; Timur Gungor; Patrick Y.S. Lam; Tammy C. Wang; Rejean Ruel; Alexandre L'Heureux; Carl Thibeault; Gilles Bouthillier; Dora M. Schnur
Archive | 2006
Hannguang J. Chao; R. Michael Lawrence; Rejean Ruel; James C. Sutton
Archive | 2017
Wei Meng; Hannguang J. Chao; Heather Finlay; Lawrence, R., Michael; Michael C. Myers
Analytical Biochemistry | 2016
Zhengping Ma; Hannguang J. Chao; Huji Turdi; Jon J. Hangeland; Todd J. Friends; Lisa M. Kopcho; R. Michael Lawrence; Dong Cheng
Archive | 2006
Hannguang J. Chao; R. Michael Lawrence; Rejean Ruel; James C. Sutton
Archive | 2017
Wei Meng; Monique Phillips; Michael C Myers; R. Michael Lawrence; James A. Johnson; Ji Jiang; Heather Finlay; Hannguang J. Chao; Soong Hoon Kim
Archive | 2017
Meng Wei; Hannguang J. Chao; Finlay Hather; R. Michael Lawrence; Michael C Myers
Archive | 2016
Ji Jiang; Monique Phillips; Hannguang J. Chao; Michael C Myers; R. Michael Lawrence; Soong Kim; James A. Johnson