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Your search keyword '"DeBono, Aaron J."' showing total 3 results
Start Over Author "DeBono, Aaron J." Publisher american chemical society
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3. Substituted Pyridazin-3(2 H)-ones as Highly Potent and Biased Formyl Peptide Receptor Agonists.

Author

Deora GS, Qin CX, Vecchio EA, Debono AJ, Priebbenow DL, Brady RM, Beveridge J, Teguh SC, Deo M, May LT, Krippner G, Ritchie RH, and Baell JB

Subjects
Blood Proteins metabolism, Calcium Signaling drug effects, Drug Discovery, HL-60 Cells, Humans, Inflammation drug therapy, Inflammation metabolism, MAP Kinase Signaling System drug effects, Phosphorylation drug effects, Protein Binding, Receptors, Lipoxin, Structure-Activity Relationship, Pyrazines chemical synthesis, Pyrazines pharmacology, Receptors, Formyl Peptide agonists
Abstract

Herein we describe the development of a focused series of functionalized pyridazin-3(2 H)-one-based formyl peptide receptor (FPR) agonists that demonstrate high potency and biased agonism. The compounds described demonstrated biased activation of prosurvival signaling, ERK1/2 phosphorylation, through diminution of the detrimental FPR1/2-mediated intracellular calcium (Ca i 2+ ) mobilization. Compound 50 showed an EC 50 of 0.083 μM for phosphorylation of ERK1/2 and an approximate 20-fold bias away from Ca i 2+ mobilization at the hFPR1.

Published
2019
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