AM-8123

AM-8123 is an orally active and potent APJ agonist. AM-8123 inhibits Forskolin-stimulated cAMP production and promotes Gα protein activation. AM-8123 can be used for the research of cardiovascular disease[1].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Others >> Others

APJ[1]

AM-8123 (100 nM) causes a rapid β-arrestin translocation from cytoplasm to plasma membrane in APJ-expressing cells. AM-8123 bound the native hAPJ receptor with low nanomolar affinity[1].

AM-8123 (100 mg/kg; p.o.) results in sustained improvement in systolic function and decreases both EDV and ESV as measured by echocardiography but not by the invasive pressure-volume conductance catheter at study termination[1]. AM-8123 (0.035, 0.09, 0.9, and 9 mg/kg; i.v.) improves cardiovascular function[1]. AM-8123 exhibits appreciably greater oral bioavailability in rats and dogs relative to pyr-apelin-13. AM-8123 infusion results in an increase in EF, SV, and dP/dt max at submicromolar unbound plasma concentrations with minimal change in HR, indicating that acute infusion of AM-8123 is associated with an improvement in several markers of cardiac function. AM-8123 is a more potent mediator of both ERK and AKT phosphorylation relative to pyr-apelin-13[1]. Animal Model: Lewis rats (2~3 months old)[1] Dosage: 100 mg/kg Administration: P.o. Result: Resulted in sustained improvement in systolic function. Decreased both EDV and ESV as measured by echocardiography but not by the invasive pressure-volume conductance catheter at study termination. Animal Model: Rats[1] Dosage: 0.035, 0.09, 0.9, and 9 mg/kg Administration: I.v. Result: Improved cardiovascular function.

[1]. Ason B, et al. Cardiovascular response to small-molecule APJ activation. JCI Insight. 2020;5(8):e132898. Published 2020 Apr 23. doi:10.1172/jci.insight.132898