A5061618319- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Protein Kinase Regulation and GTPase Signaling
- NF-κB Signaling Pathways
- Computational Drug Discovery Methods
- Biochemical Acid Research Studies
- Carbohydrate Chemistry and Synthesis
- Cell Adhesion Molecules Research
- Mass Spectrometry Techniques and Applications
- Mitochondrial Function and Pathology
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Metabolism and Genetic Disorders
- interferon and immune responses
- Metabolism, Diabetes, and Cancer
- Diabetes Treatment and Management
- Machine Learning and Data Classification
- Blood Coagulation and Thrombosis Mechanisms
- Phosphodiesterase function and regulation
- Click Chemistry and Applications
- Immunotherapy and Immune Responses
- Biochemical and Structural Characterization
- Amino Acid Enzymes and Metabolism
- ATP Synthase and ATPases Research
Merck & Co., Inc., Rahway, NJ, USA (United States)
2010-2017
University of New Brunswick
2010
The University of Texas at Austin
1989-1996
5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite three decades investigation, the biological roles AMPK and its potential as drug target remain incompletely understood, largely because lack optimized pharmacological tools. We developed MK-8722, potent, direct, allosteric activator all 12 mammalian complexes. In rodents rhesus monkeys, MK-8722-mediated activation skeletal muscle induced robust, durable,...
Protein ectodomain shedding is crucial for cell–cell interactions because it controls the bioavailability of soluble tumor necrosis factor-α (TNFα) and ligands epidermal growth factor (EGF) receptor, release many other membrane proteins. Various stimuli can rapidly trigger shedding, yet much remains to be learned about identity enzymes that respond these mechanisms underlying their activation. Here, we demonstrate membrane-anchored metalloproteinase ADAM17, but not ADAM10, sheddase responds...
IRAK4 is a critical upstream kinase in the IL-1R/TLR signaling pathway. Inhibition of hypothesized to be beneficial treatment autoimmune related disorders. A screening campaign identified pyrazole class inhibitors that were determined by X-ray crystallography exhibit an unusual binding mode. SAR efforts focused on identification potent and selective inhibitor with good aqueous solubility rodent pharmacokinetics. Pyrazole C-3 piperidines well tolerated, N-sulfonyl analogues generally having...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExpression, Purification, and Characterization of the Dihydrolipoamide Dehydrogenase-Binding Protein Pyruvate Dehydrogenase Complex from Saccharomyces cerevisiaeCheol-Young Maeng, Mohammad A. Yazdi, Xiao-Da Niu, Hoi Y. Lee, Lester J. ReedCite this: Biochemistry 1994, 33, 46, 13801–13807Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue 1 November...
Semi-supervised classification methods utilize unlabeled data to help learn better classifiers, when only a small amount of labeled is available. Many semi-supervised learning have been proposed in the past decade. However, some questions not well answered, e.g., whether outperform base classifiers learned from data, different are used, selecting with efforts superior random selection, and how quality classifier changes at each iteration process. This paper conducts an extensive empirical...
We report the identification and synthesis of a series aminopyrimidin-4-one IRAK4 inhibitors. Through high throughput screening, an aminopyrimidine hit was identified modified via structure enabled design to generate new, potent, kinase selective pyrimidin-4-one chemotype. This chemotype is exemplified by compound 16, which has potent inhibition activity (IC50 = 27 nM) excellent selectivity (>100-fold against 99% 111 tested kinases), 31, displays 93 good rat bioavailability (F 42%).
Through a de novo design approach, hydroxamates derived from trans-cyclopropyl dicarboxylate were examined as potential TNF-alpha converting enzyme (TACE) inhibitors. Two distinctive series of inhibitors (A and B) identified shown to have different structure-activity relationship trends selectivity profiles against other matrix metalloproteases despite their close structural similarities. X-ray crystallography the binding TACE demonstrates that each derives its activity opposite enantiomer...