Epidermal growth factor receptor (EGFR) is a transmembrane protein and a member of the ErbB receptor family. Specifically, EGFR is a tyrosine kinase in various tissues and mediates cell proliferation, differentiation, migration, and survival. Besides, the activation of EGFR in a ligand-dependent or ligand-independent manner can lead to homodimerization or heterodimerization of related family members.
EGFR is the target of cancer treatment and can participate in non-malignant chronic diseases. In the cardiovascular system, EGFR and its ligands play a complex role in the regulation of a variety of cell behaviors. Moreover, the EGFR signaling pathway is important in both normal and pathological states. Moreover, studies have shown that EGFR antagonism may be an effective drug target for cardiac hypertrophy and remodeling. Here, we will introduce a selective EGFR tyrosine kinase inhibitor, AG-1478.
AG-1478 is a selective EGFR tyrosine kinase inhibitor.
First of all, AG-1478 is a selective EGFR tyrosine kinase inhibitor with IC50 of 3 nM. Particularly, AG-1478 has antiviral effects against HCV and encephalomyocarditis virus (EMCV).
In the second place, AG-1478 is irreversible for the growth regulation of human lung (A549) and prostate (DU145) cancer cell lines. Particularly, AG-1478 significantly reduced the synthesis of TGF-β and fibronectin mediated by angiotensin II in cardiac fibroblasts. Meanwhile, AG-1478 significantly induced apoptosis in HEK 293 cells.
Last but not the least, AG-1478 (10 mg/kg/day) by oral gavage significantly reduces myocardial inflammation, fibrosis, apoptosis, and dysfunction in ApoE-/- mice with HFD. Importantly, AG-1478 blocks HFD induced cardiac EGFR phosphorylation in vivo. Additionally, AG-1478 blocked EGF (10 nM)-induced a robust and reproducible elevation in EGFR phosphorylation.
All in all, AG-1478 is a selective EGFR tyrosine kinase inhibitor.
Li W, et al. Sci Rep. 2016 Apr 18;6:24580.