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Your search keyword '"Zhao, Shi Feng"' showing total 4 results
Start Over Author "Zhao, Shi Feng" Publisher american chemical society
4 results on '"Zhao, Shi Feng"'

4. Discovery of Chromane-6-Sulfonamide Derivative as a Potent, Selective, and Orally Available Novel Retinoic Acid Receptor-Related Orphan Receptor γt Inverse Agonist.

Author

Chen L, Su M, Jin Q, Wang W, Wang CG, Assani I, Wang MX, Zhao SF, Lv SM, Wang JW, Sun B, Li Y, and Liao ZX

Subjects
Animals, Cyclization, Humans, Jurkat Cells, Mice, Molecular Docking Simulation, Pyrans administration & dosage, Pyrans chemistry, Structure-Activity Relationship, Sulfonamides administration & dosage, Sulfonamides chemistry, Chromans chemistry, Drug Delivery Systems, Nuclear Receptor Subfamily 1, Group F, Member 3 agonists, Pyrans pharmacology, Sulfonamides pharmacology
Abstract

Interleukin-17 (IL-17) is a proinflammatory cytokine that plays a dominant role in inflammation, autoimmunity, and host defense. RORγt is a key transcription factor mediating T helper 17 (Th17) cell differentiation and IL-17 production, which is able to activate CD8 + T cells and elicit antitumor efficacy. A series of sulfonamide derivatives as novel RORγt inverse agonists were designed and synthesized. Using GSK2981278 (phase II) as a starting point, we engineered structural modifications that significantly improved the activity and pharmacokinetic profile. In animal studies, oral administration of compound d3 showed a robust and dose-dependent inhibition of the IL-17A cytokine expression in a mouse imiquimod-induced skin inflammation model. Docking analysis of the binding mode revealed that the compound d3 occupied the active pocket suitably. Thus, compound d3 was selected as a clinical compound for the treatment of Th17-driven autoimmune diseases.

Published
2021
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