Discoidin domain receptor family (DDRs)

The Discoidin Domain Receptor (DDR) family consists of two unique receptor tyrosine kinases, DDR1 and DDR2, which are activated by various types of collagen rather than soluble growth factors (Leitinger, 2014, Reproduction). DDR1 is primarily expressed in epithelial cells, while DDR2 is found in mesenchymal cells such as fibroblasts and chondrocytes (Valiathan et al., 2012, Cancer Metastasis Rev). These receptors play critical roles in sensing the extracellular matrix environment and regulating cell adhesion, migration, and proliferation (Rammal et al., 2016, Cancers). Dysregulation of DDR signaling is strongly linked to the progression of various cancers, where it promotes epithelial-mesenchymal transition (EMT) and metastasis, as well as fibrotic diseases and chronic inflammation (Moll et al., 2019, Trends in Molecular Medicine). Several multi-kinase inhibitors originally developed for other targets, such as Nilotinib and Dasatinib, have been found to potently inhibit DDRs, and specific DDR inhibitors are currently under investigation for their therapeutic potential in oncology and fibrotic disorders (Bennasroune et al., 2019, International Journal of Molecular Sciences).

Other names

Discoidin domain-containing receptorsCollagen-activated receptor tyrosine kinasesCD167Tyrosine-protein kinase DDR1Tyrosine-protein kinase DDR2

Small molecule inhibition of the intracellular kinase domain to block collagen-induced autophosphorylation and downstream signaling pathways such as MAPK/ERK and PI3K/Akt.