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In Vitro and In Vivo Evaluation of a Small-Molecule APJ (Apelin Receptor) Agonist, BMS-986224, as a Potential Treatment for Heart Failure

Circ Heart Fail. 2021-03; 
Peter Gargalovic, Pancras Wong, Joelle Onorato, Heather Finlay, Tao Wang, Mujing Yan, Earl Crain, Stéphane St-Onge, Madeleine Héroux, Michel Bouvier, Carrie Xu, Xue-Qing Chen, Claudia Generaux, Michael Lawrence, Ruth Wexler, David Gordon
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Recombinant Proteins … upon request. In Vitro Characterization Studies. (Pyr 1 ) apelin-13 (GenScript) and BMS-986224 (synthesized by Bristol Myers Squibb) were used in the in vitro experiments. [ 3 H] Apelin-13 Radioligand Binding Assays. Stable?… Get A Quote

摘要

background: New heart failure therapies that safely augment cardiac contractility and output are needed. Previous apelin peptide studies have highlighted the potential for APJ (apelin receptor) agonism to enhance cardiac function in heart failure. However, apelin's short half-life limits its therapeutic utility. Here, we describe the preclinical characterization of a novel, orally bioavailable APJ agonist, BMS-986224. methods: BMS-986224 pharmacology was compared with (Pyr) apelin-13 using radio ligand binding and signaling pathway assays downstream of APJ (cAMP, phosphorylated ERK [extracellular signal-regulated kinase], bioluminescence resonance energy transfer-based G-protein assays, β-arrestin recruitment,... More

關鍵詞

apelin, heart failure, hemodynamics, ligands, signal transduction
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