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Your search keyword '"Ryan, Moslin"' showing total 2 results
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2 results on '"Ryan, Moslin"'

1. Identification of

Author

Ryan, Moslin, Yanlei, Zhang, Stephen T, Wrobleski, Shuqun, Lin, Michael, Mertzman, Steven, Spergel, John S, Tokarski, Joann, Strnad, Kathleen, Gillooly, Kim W, McIntyre, Adriana, Zupa-Fernandez, Lihong, Cheng, Huadong, Sun, Charu, Chaudhry, Christine, Huang, Celia, D'Arienzo, Elizabeth, Heimrich, Xiaoxia, Yang, Jodi K, Muckelbauer, ChiehYing, Chang, Jeffrey, Tredup, Dawn, Mulligan, Dianlin, Xie, Nelly, Aranibar, Manoj, Chiney, James R, Burke, Louis, Lombardo, Percy H, Carter, and David S, Weinstein

Subjects
Niacinamide, TYK2 Kinase, Mice, Structure-Activity Relationship, Allosteric Regulation, Nicotinic Acids, Animals, Humans, Ligands, Protein Kinase Inhibitors
Abstract

As a member of the Janus (JAK) family of nonreceptor tyrosine kinases, TYK2 plays an important role in mediating the signaling of pro-inflammatory cytokines including IL-12, IL-23, and type 1 interferons. The nicotinamide

Published
2019

2. Identification of Imidazo[1,2

Author

Chunjian, Liu, James, Lin, Ryan, Moslin, John S, Tokarski, Jodi, Muckelbauer, ChiehYing, Chang, Jeffrey, Tredup, Dianlin, Xie, Hyunsoo, Park, Peng, Li, Dauh-Rurng, Wu, Joann, Strnad, Adriana, Zupa-Fernandez, Lihong, Cheng, Charu, Chaudhry, Jing, Chen, Cliff, Chen, Huadong, Sun, Paul, Elzinga, Celia, D'arienzo, Kathleen, Gillooly, Tracy L, Taylor, Kim W, McIntyre, Luisa, Salter-Cid, Louis J, Lombardo, Percy H, Carter, Nelly, Aranibar, James R, Burke, and David S, Weinstein

Abstract

[Image: see text] In sharp contrast to a previously reported series of 6-anilino imidazopyridazine based Tyk2 JH2 ligands, 6-((2-oxo-N1-substituted-1,2-dihydropyridin-3-yl)amino)imidazo[1,2-b]pyridazine analogs were found to display dramatically improved metabolic stability. The N1-substituent on 2-oxo-1,2-dihydropyridine ring can be a variety of alkyl, aryl, and heteroaryl groups, but among them, 2-pyridyl provided much enhanced Caco-2 permeability, attributed to its ability to form intramolecular hydrogen bonds. Further structure–activity relationship studies at the C3 position led to the identification of highly potent and selective Tyk2 JH2 inhibitor 6, which proved to be highly effective in inhibiting IFNγ production in a rat pharmacodynamics model and fully efficacious in a rat adjuvant arthritis model.

Published
2019

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