The discoidin domain receptors DDR1 and DDR2 are structurally related receptor tyrosine kinases that function as collagen receptors. The 28 different collagens form the most abundant protein family in man. Collagens are found in the extracellular matrix and are generally deposited there in the form of supramolecular assemblies arranged from triple-helical rope-like structural units. In man, the main collagens include COL1A1 (COL1A1, P02452), COL2A1 (COL2A1, P02458), COL3A1 (COL3A1, P02461) and COL4A1 (COL4A1, P02462).

Other collagen receptors include four collagen-binding integrins of the β1 integrin family (ITGB1, P05556), with the following α subunits: α1 (ITGA1, P56199), α2 (ITGA2, P17301), α10 (ITGA10, O75578) or α11 (ITGA11, Q9UKX5). Additional collagen receptors include, glycoprotein VI (GP6, Q9HCN6), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1, Q6GTX8), leukocyte-associated immunoglobulin-like receptor 2 (LAIR2, Q6ISS4) and osteoclast-associated immunoglobulin-like receptor (OSCAR, Q8IYS5).
The tyrosine kinase inhibitors of DDR, imatinib and nilotinib, were identified from proteomic analysis [2].

1. Carafoli F, Mayer MC, Shiraishi K, Pecheva MA, Chan LY, Nan R, Leitinger B, Hohenester E. (2012) Structure of the discoidin domain receptor 1 extracellular region bound to an inhibitory Fab fragment reveals features important for signaling. Structure, 20 (4): 688-97. [PMID:22483115]

2. Day E, Waters B, Spiegel K, Alnadaf T, Manley PW, Buchdunger E, Walker C, Jarai G. (2008) Inhibition of collagen-induced discoidin domain receptor 1 and 2 activation by imatinib, nilotinib and dasatinib. Eur J Pharmacol, 599 (1-3): 44-53. [PMID:18938156]

3. Gao M, Duan L, Luo J, Zhang L, Lu X, Zhang Y, Zhang Z, Tu Z, Xu Y, Ren X et al.. (2013) Discovery and optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as novel selective and orally bioavailable discoidin domain receptor 1 (DDR1) inhibitors. J Med Chem, 56 (8): 3281-95. [PMID:23521020]

4. Kim HG, Tan L, Weisberg EL, Liu F, Canning P, Choi HG, Ezell SA, Wu H, Zhao Z, Wang J et al.. (2013) Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor. ACS Chem Biol, 8 (10): 2145-50. [PMID:23899692]

5. Liu J, Chiang HC, Xiong W, Laurent V, Griffiths SC, Dülfer J, Deng H, Sun X, Yin YW, Li W et al.. (2023) A highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer. J Immunother Cancer, 11 (6). [PMID:37328286]