Eph family receptor tyrosine kinases (Eph receptors) (Eph)

The Eph family receptor tyrosine kinases (Eph receptors) constitute the largest subfamily of receptor tyrosine kinases in the human genome, comprising 14 members divided into EphA and EphB subclasses (Wikipedia, 2023; NIH, 2015). These receptors are unique for their ability to mediate contact-dependent bidirectional signaling upon interaction with membrane-bound ligands called ephrins, influencing both the receptor-expressing cell (forward signaling) and the ligand-expressing cell (reverse signaling) (NIH, 2013; Annual Reviews, 2015). Biologically, they play critical roles in embryonic development, including axon guidance, tissue patterning, and angiogenesis, while in adults, they maintain tissue homeostasis and regulate immune responses (NIH, 2024; Frontiers, 2021). In disease, Eph receptors are frequently dysregulated; they can act as either tumor promoters or suppressors depending on the context and are implicated in various cancers, neurological disorders, and fibrosis (MDPI, 2021; Encyclopedia.pub, 2021; Patsnap, 2024). Therapeutic strategies targeting this family include monoclonal antibodies, antibody-drug conjugates, and small-molecule kinase inhibitors like dasatinib (NIH, 2009; MedChemExpress, 2024). However, the complex dual roles of these receptors in cancer and their widespread expression in normal tissues present significant challenges for drug development and clinical safety (MDPI, 2021; NIH, 2015).

Other names

Erythropoietin-producing hepatocellular carcinoma receptorsEphrin receptorsEphsEph RTKs

The primary mechanisms of action for drugs targeting Eph receptors include the inhibition of the intracellular tyrosine kinase domain to block forward signaling, the use of monoclonal antibodies to induce receptor internalization and degradation, and the application of soluble decoy receptors to sequester ephrin ligands (Patsnap, 2024; MedChemExpress, 2024; NIH, 2015). Additionally, some agents work by competitively blocking the ligand-binding domain to prevent bidirectional signaling (NIH, 2013; Cancer.gov, 2021).