Discoidin domain receptor (DDR (also DDR1 and DDR2 for specific family members))

Discoidin domain receptors are a unique subgroup of receptor tyrosine kinases comprising DDR1 and DDR2, which are activated by binding to various types of collagen in the extracellular matrix[1][2][3][7]. Unlike most RTKs that are stimulated by soluble peptide ligands, DDRs serve as sensors of collagen and mediate slow, sustained signaling upon ligand exposure[1][3][7]. They are involved in key cellular processes such as adhesion, migration, proliferation, differentiation, survival, and matrix remodeling[3][7]. DDRs play physiological roles in embryonic development and tissue homeostasis but are also implicated in pathological conditions including multiple cancers, fibrosis, and inflammatory diseases[7][9][10]. Clinically, DDR overexpression or mutations are observed in several malignancies and fibrotic diseases, making them attractive targets for therapeutic intervention and disease biomarkers[7][10]. Currently, multiple broad-spectrum kinase inhibitors target DDRs, but the search for selective DDR inhibitors is ongoing[7].

Other names

DDRDDR1 (Discoidin domain receptor family, member 1)DDR2 (Discoidin domain receptor family, member 2)Cluster of differentiation 167a (CD167a, for DDR1)Cluster of differentiation 167b (CD167b, for DDR2)Receptor tyrosine kinase DDR1Receptor tyrosine kinase DDR2

Inhibition of receptor tyrosine kinase activity (prevents phosphorylation and downstream signaling) Interference with collagen-binding and subsequent cellular effects