Discoidin domain receptor tyrosine kinase (DDR kinase) (DDR1, DDR2)

Discoidin domain receptor kinases are collagen-binding receptor tyrosine kinases comprising DDR1 and DDR2. Both are single-pass transmembrane proteins featuring a distinctive extracellular discoidin domain, enabling collagen recognition. Upon binding collagen, DDRs dimerize and autophosphorylate, launching downstream signaling that affects cell differentiation, proliferation, adhesion, migration, and extracellular matrix remodeling. DDRs are key regulators of fibrosis and cancer progression, and their expression is elevated in various tumors and fibrotic diseases. DDR kinase inhibitors (e.g., RXC009, REDX12271, and certain clinical kinase inhibitors) are under development as specific anti-fibrotic and anti-tumor agents. Selectivity, safety, and efficacy remain ongoing challenges in drug development.

Other names

CD167adiscoidin domain receptor family, member 1CD167bneurotrophic tyrosine kinase receptor-related 3TYRO10NTRKR3

Inhibition of DDR1/DDR2 kinase autophosphorylation blocks collagen-induced signal transduction, cell proliferation, migration, and fibrosis. Synthetic lethality by combining DDR inhibition with other pathway inhibitors (under investigation for cancer)