Epithelial discoidin domain-containing receptor 1 (DDR1)

Epithelial discoidin domain-containing receptor 1 (DDR1) is a unique member of the receptor tyrosine kinase (RTK) family that is activated by various types of collagen rather than soluble growth factors [1, 5, 13]. Primarily expressed in epithelial cells, DDR1 serves as a non-integrin collagen receptor that mediates critical interactions between cells and the extracellular matrix (ECM) [1, 8]. Upon activation by collagen binding, DDR1 triggers signaling pathways involving SRC and MAP kinases that regulate cell adhesion, migration, and matrix remodeling [1, 8, 9]. In oncology, DDR1 is frequently overexpressed and acts as an oncogenic driver, promoting tumor cell survival, invasion, and the exclusion of immune cells from the tumor microenvironment [8, 20, 21]. Beyond cancer, DDR1 is a significant therapeutic target in fibrotic and inflammatory diseases, where its dysregulation contributes to pathological tissue scarring in organs such as the lungs, liver, and kidneys [8, 9, 10]. Current drug development efforts focus on selective small-molecule inhibitors and monoclonal antibodies to disrupt its pro-tumorigenic and pro-fibrotic signaling [7, 16, 18].

Other names

CD167aCell adhesion kinase (CAK)Discoidin receptor tyrosine kinaseMammary carcinoma kinase 10 (MCK10)Neurotrophic tyrosine kinase receptor-related 4 (NTRK4)Protein tyrosine kinase 3 (PTK3)Receptor tyrosine kinase 6 (RTK6)Tyrosine kinase receptor E (TRKE)HGK2

Competitive inhibition of the ATP-binding site within the DDR1 kinase domain to block autophosphorylation and downstream signaling pathways.