ERBB4 agonist EF-1 is a specific small molecule ERBB4 (HER4) agonist that induce ERBB4 homodimerization with EC50 of 10.5 uM in ERBB4/ERBB4 dimerization assay, reduces cell death and hypertrophy in cardiomyocytes and decreases collagen production in cardiac fibroblasts.
EF-1 displays little to no stimulatory effect on ERBB2/ERBB3 heterodimerization at higher concentrations (EC50>32 uM).
EF-1 dose-dependently and significantly potentiates NRG1-induced ERBB4 homodimerization by 299.5% at 32 uM.
EF-1 induces a time-dependent phosphorylation of Akt in cardiomyogenically differentiated immortalized rat atrial myocytes (iAMs).
EF-1 and NRG1 activate similar downstream signaling pathways in human cultured cardiac fibroblasts, downregulates the transforming growth factor-β (TGF-β) and MAPK/ERK pathways.
EF-1 decreases TGF-β1-induced collagen expression through ERBB4 in vitro, decreases COL3A1 mRNA levels.
EF-1 reduces cardiomyocyte cell death and hypertrophy in vitro.
EF-1 prevents cardiac fibrosis in mouse model of AngII-induced myocardial fibrosis, does not significantly alter cardiac dimensions on ultrasound.
EF-1 prevented cardiomyocyte injury in doxorubicin (DOX)-treated mice, reduces cardiac remodeling and interstitial fibrosis after MI.