APJ Receptor Agonist 4 is a potent, orally active apelin receptor (APJ) agonist, demonstrating an EC50 of 0.06 nM and a Ki of 0.07 nM. It exhibits excellent pharmacokinetic profiles in rodent heart failure (HF) models and has shown an acceptable safety profile in preclinical toxicology studies. This compound effectively improves cardiac function, making it valuable for research into HF disease.

Assessment of Pharmacokinetics (PK) profile of APJ receptor agonist 4 (compound 21) in mouse[1]. species rat monkey dog max (ng/mL) dose (mg/kg) 1 (i.v. and p.o.) 1 (i.v.) and 3 (p.o.) 1 (i.v. and p.o.) vehiclea F G G CI (mL/min/kg) 4.6 10.6 2.4 V SS (L/kg) 1.6 0.2 0.2 T 1/2 (h) 4.0 1.3 2.5 C max (μM?h) 2.2 1.4 6.5 AUC 0-24 (μM?h) 3.7 2.5 14.2 F (%) 54 27 76 a: Vehicle F: 5/5/90 v/v/v DMAC/Cremophor EL/sodium carbonate buffer, pH 9 and vehicle G: 10/40/50 v/v/v ethanol/PEG400/sodium carbonate buffer, pH 9.