Mark Kirby

Discovery of liver-selective glucokinase activators comprising N-(4-alkylthiazol-2-yl)benzamides and N-(3-alkyl-1,2,4-thiadiazol-5-yl)benzamides for the treatment of metabolic disorders

David Yoon, Shung Wu, Rebecca A. Smirk, Robert Brigance et autres

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Topological fidelity of additively manufactured AlSi10Mg gyroid structures

Osezua Ibhadode, Issa Rishmawi, Mark Kirby, Mihaela Vlasea et autres

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Discovery of a Partial Glucokinase Activator Clinical Candidate: Diethyl ((3-(3-((5-(Azetidine-1-carbonyl)pyrazin-2-yl)oxy)-5-isopropoxybenzamido)-1H-pyrazol-1-yl)methyl)phosphonate (BMS-820132)

Yan Shi, Wang Ying, Wei Meng, Robert Brigance et autres

Glucokinase (GK) is a key regulator of glucose homeostasis, and its small-molecule activators represent a promising opportunity for the treatment of type 2 diabetes. Several GK activators have been advanced into clinical trials and have demonstrated promising efficacy; however, hypoglycemia represents a …

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The Additive Journey from Powder to Part

Yanli Zhu, Ahmet Okyay, Mihaela Vlasea, Kaan Erkorkmaz et autres

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Genetic Control of Obesity and Gut Microbiota Composition in Response to High-Fat, High-Sucrose Diet in Mice

Elin Org, Brian W. Parks, Mark Kirby, Aiqing He et autres

Obesity is a highly heritable disease driven by complex interactions between genetic and environmental factors. Human genome-wide association studies (GWAS) have identified a number of loci contributing to obesity; however, a major limitation of these studies is the inability to assess environmental …

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Furnishing Sir Christopher Wren's churches: Anglican identity in late-seventeenth century London

Mark Kirby

This thesis examines what the liturgical furnishings of Sir Christopher Wren’s churches can tell us about Anglican identity in late seventeenth-century London. It argues that the building of so many churches in a short timescale gave the Church of England a unique …

A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis

Yue Xiao, Xikun Wu, Lichun Jiang, Shurong Yang et autres

BACKGROUND: Noninvasive biomarkers are urgently needed for patients with nonalcoholic steatohepatitis (NASH) to assist in diagnosis, monitoring disease progression and assessing treatment response. Recently several exploratory studies showed that circulating level of microRNA is associated with NASH and correlated with disease severity. …

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Discovery of Clinical Candidate 2-((2S,6S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3′-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor

Xiang‐Yang Ye, Stephanie Chen, Shung Wu, David Yoon et autres

BMS-816336 ( 6n-2 ), a hydroxy-substituted adamantyl acetamide, has been identified as a novel, potent inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme (IC 50 3.0 nM) with >10000-fold selectivity over human 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). 6n-2 exhibits a robust …

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Utilization of the Zucker Diabetic Fatty (ZDF) Rat Model for Investigating Hypoglycemia-related Toxicities

Mark A. Tirmenstein, Joseph Horvath, Michael J. Graziano, Raja S. Mangipudy et autres

Glucokinase (GK) catalyzes the initial step in glycolysis and is a key regulator of glucose homeostasis. Therefore, glucokinase activators (GKa) have potential benefit in treating type 2 diabetes. Administration of a Bristol-Myers Squibb GKa (BMS-820132) to healthy euglycemic Sprague-Dawley (SD) rats and …

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Synthesis and structure–activity relationship of 2-adamantylmethyl tetrazoles as potent and selective inhibitors of human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)

Xiang‐Yang Ye, David Yoon, Stephanie Chen, Akbar Nayeem et autres

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Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778)

Pratik Devasthale, Ying Wang, Wei Wang, John M. Fevig et autres

Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. …

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DPP8 and DPP9 expression in cynomolgus monkey and Sprague Dawley rat tissues

Eric B. Harstad, Jonathan S. Rosenblum, Mark D. Gorrell, William E. Achanzar et autres

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