Discoidin domain receptor family member 1 (DDR1)

Discoidin domain receptor family member 1 (DDR1) is a unique member of the receptor tyrosine kinase (RTK) superfamily that is activated by various types of collagen rather than soluble growth factors [1, 4]. Primarily expressed in epithelial cells, DDR1 serves as a critical sensor of the extracellular matrix, regulating fundamental cellular processes such as adhesion, proliferation, migration, and matrix remodeling [4, 8]. Upon binding to collagen, DDR1 undergoes a characteristically slow and sustained autophosphorylation, which triggers downstream signaling pathways including the MAPK/ERK and PI3K/Akt cascades [10, 13]. In pathological contexts, DDR1 is frequently overexpressed or mutated, contributing significantly to the progression of numerous cancers by promoting invasion, metastasis, and resistance to therapy [14, 15]. Beyond oncology, DDR1 plays a pivotal role in the pathogenesis of fibrotic diseases, atherosclerosis, and neurodegenerative disorders like Parkinson's disease, where it modulates neuroinflammation and protein clearance [2, 16]. Consequently, DDR1 has emerged as a promising therapeutic target, with several clinical-stage multi-kinase inhibitors like nilotinib and dasatinib showing potent inhibitory activity against it [1, 7, 12].

Other names

DDREDDR1MCK10NTRK4PTK3ARTK6TRKECD167aCell adhesion kinaseTyrosine-protein kinase DDR1

Tyrosine kinase inhibition via competitive binding to the ATP-binding site in either active (Type I) or inactive (Type II) conformations, thereby preventing collagen-induced autophosphorylation and downstream signaling.