Angiopoietin-1 receptor (TEK) (Tie2)

The Angiopoietin-1 receptor (TEK), commonly known as Tie2, is a transmembrane receptor tyrosine kinase primarily expressed on endothelial cells and hematopoietic stem cells (UniProt: P35590). It plays a critical role in vascular development and maintenance by interacting with its ligands, Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) (PubMed: 24503118). Ang-1 acts as a potent agonist that promotes vessel maturation and stability, whereas Ang-2 often acts as a context-dependent antagonist that destabilizes vessels to allow for remodeling or pathological angiogenesis (PubMed: 10359826). In diseases like cancer and neovascular age-related macular degeneration, the Tie2 pathway is dysregulated, often characterized by high levels of Ang-2 leading to vascular leakage and inflammation (PubMed: 28258190). Therapeutic strategies include bispecific antibodies like faricimab, which inhibits both VEGF and Ang-2 to stabilize the retinal vasculature, and small molecule multi-kinase inhibitors like regorafenib that target the Tie2 kinase domain to inhibit tumor angiogenesis (FDA Label: Vabysmo; PubMed: 23062801).

Other names

TEKTIE2CD202BVMCMVMCM1Tyrosine-protein kinase receptor TEKTunica interna endothelial cell kinase

Drugs targeting the Tie2 pathway primarily function by either inhibiting the Tie2 tyrosine kinase activity, neutralizing the destabilizing ligand Ang-2 to restore Tie2 signaling, or directly activating the Tie2 receptor to promote vascular stability and reduce permeability (PubMed: 24503118, 28258190).