DDR2
DDR2 (discoidin domain receptor 2) is a collagen-activated receptor tyrosine kinase that regulates cell-collagen interactions in normal and pathological tissue contexts[1]. Mechanistically, type I collagen activates DDR2 and promotes Src and Shc signaling, linking extracellular matrix sensing to intracellular phosphorylation responses[2]. In cartilage disease models, DDR2 activation induces MMP-13, connecting collagen receptor signaling with matrix degradation in osteoarthritis-related cartilage damage[3]. In breast cancer models, collagen I-activated DDR2 stabilizes SNAIL1 through Src-dependent ERK2 activity, supporting invasion, migration, epithelial-mesenchymal transition, and metastasis[4]. Compared with related isoforms, DDR1 is mainly associated with epithelial cells, whereas DDR2 is mainly associated with mesenchymal cells, making DDR2 especially relevant to fibroblast-rich stroma, cartilage, and collagen-dense tumor microenvironments[1]. In lung squamous cell carcinoma, DDR2 kinase mutations occur in a defined patient subset and confer sensitivity to Dasatinib (HY-10181) in experimental models[5]. For experimental applications, the extracellular allosteric inhibitor WRG-28 blocks DDR2-collagen interaction, inhibits tumor invasion and migration, and reduces metastatic breast tumor cell colonization in lungs[6].
References:
- [1]. Fu HL, et al. Discoidin domain receptors: unique receptor tyrosine kinases in collagen-mediated signaling. J Biol Chem. 2013 Mar 15;288(11):7430-7437. [Content Brief]
- [2]. Ikeda K, et al. Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen. J Biol Chem. 2002 May 24;277(21):19206-12. [Content Brief]
- [3]. Xu L, et al. Activation of the discoidin domain receptor 2 induces expression of matrix metalloproteinase 13 associated with osteoarthritis in mice. J Biol Chem. 2005 Jan 7;280(1):548-55. [Content Brief]
- [4]. Zhang K, et al. The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis. Nat Cell Biol. 2013 Jun;15(6):677-87. [Content Brief]
- [5]. Hammerman PS, et al. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 2011 Jun;1(1):78-89. [Content Brief]
- [6]. Grither WR, et al. Inhibition of tumor-microenvironment interaction and tumor invasion by small-molecule allosteric inhibitor of DDR2 extracellular domain. Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7786-E7794. [Content Brief]
-
DDR2 Related Products (17)
-
Recombinant Proteins (10)
- 1
-
Sitravatinib
0 ImagesSynonyms: MGCD516; MG-516Sitravatinib (MGCD516) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC50s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively. Sitravatinib shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment.
-
WRG-28
0 ImagesWRG-28 is a selective, extracellularly acting DDR2 allosteric inhibitor, with an IC50 of 230 nM. WRG-28 inhibits tumor invasion, migration and tumor-supporting effects of cancer-associated fibroblasts (CAFs). WRG-28 inhibits metastatic breast tumor cell colonization in the lungs. WRG-28 also shows good activity of relieving rheumatoid arthritis in CAIA model of mice.
-
VU6015929
0 ImagesVU6015929 is a potent, selective and orally active dual discoidin domain receptor 1/2 (DDR1/2) inhibitor with IC50s of 4.67 nM and 7.39 nM, respectively. VU6015929 potently blocks collagen-induced DDR1 activation and collagen-IV production.
-
DDR1-IN-4
0 ImagesDDR1-IN-4 (Compound 2.45) is a selective and potent Discoidin Domain Receptor 1 (DDR1) autophosphorylation inhibitor, with IC50 values of 29 nM and 1.9 μM for DDR1 and DDR2, respectively.
-
Collagen (bovine skin)
0 ImagesCollagen (bovine skin) is a three-dimensional cell culture matrix and morphoregulator extracted from bovine skin, which binds to integrins (such as α1β1, α2β1, α11β1) and discoidin domain receptors (DDR1 and DDR2). Collagen (bovine skin) can be reconstituted into a three-dimensional fibrous network to mimic the in vivo tissue environment. It can not only be modified through cross-linking or concentration adjustment, but also interact with fibronectin to enhance matrix-associated cellular activities. Collagen (bovine skin) mediates the proliferation, aggregation, durotactic migration and differentiation of fibroblasts, regulates the synthesis, remodeling and contraction of extracellular matrix, and modulates the expression, activation of MMP as well as cell apoptosis, etc. Collagen (bovine skin) can be used in studies related to the mechanisms of cancer occurrence and development.
-
Anti-Mouse DDR2 Antibody (DAB0065)
0 ImagesCat. No.: HY-P992066Anti-Mouse DDR2 Antibody (DAB0065) is a mAb that specifically targets mouse discoidin domain receptor DDR2 without cross-reacting with DDR1. Anti-Mouse DDR2 Antibody (DAB0065) binds to the extracellular domain of native mouse DDR2, induces endocytosis and lysosomal degradation of DDR2, and this process is independent of collagen binding. Anti-Mouse DDR2 Antibody (DAB0065) exhibits significant therapeutic effects in both the unilateral ureteral obstruction (UUO) mouse model of renal fibrosis and the bleomycin (HY-108345)-induced mouse model of pulmonary fibrosis, effectively downregulating the mRNA expression of type I collagen Col1a1 and fibronectin Fn1. Anti-Mouse DDR2 Antibody (DAB0065) can be humanized and has the potential to be developed as a targeted agent for diseases such as idiopathic pulmonary fibrosis and renal fibrosis.
-
DDR1/2 IN-4
0 ImagesCat. No.: HY-181839CAS No.: 3027967-95-6DDR1/2 IN-4 (Compound 37) is a selective dual DDR1 and DDR2 kinase inhibitor, with a pKi of 8.6 for DDR1 and a pKi of 8.2 for DDR2. DDR1/2 IN-4 functionally inhibits the kinase activities of DDR1 and DDR2. DDR1/2 IN-4 inhibits the release of MCP-1. DDR1/2 IN-4 can be used in studies related to idiopathic pulmonary fibrosis.
-
FGFR1/DDR2 inhibitor 1
0 ImagesFGFR1/DDR2 inhibitor 1 is an orally active inhibitor of fibroblast growth factor receptor 1 (FGFR1) and discoindin domain receptor 2 (DDR2), with IC50 values of 31.1 nM and 3.2 nM, respectively. Antitumor activity.
-
SR-302
0 ImagesSR-302, a chemical probe, is a potent and selectivity DDR/p38 inhibitor, with IC50 values of 0.125, 0.023 and 0.018 μM for p38α, DDR1 and DDR2, respectively. SR-302 can be used for the research of fibrotic disorders, such as renal and pulmonary fibrosis, atherosclerosis, and various forms of cancer.
-
CIDD-8633
0 ImagesCat. No.: HY-175202CAS No.: 1428356-95-9
-
Sitravatinib malate
0 ImagesCat. No.: HY-16961ACAS No.: 2244864-88-6Synonyms: MGCD516 malate; MG-516 malateSitravatinib malate (MGCD516 malate) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC50s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively. Sitravatinib malate shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment.
-
ML786 dihydrochloride
0 ImagesCat. No.: HY-14979ACAS No.: 1237536-18-3ML786 dihydrochloride is a potent and orally bioavailable Raf inhibitor, with IC50s of 2.1, 4.2, and 2.5 nM for V600EΔB-Raf, wt B-Raf, and C-Raf, respectively. ML786 dihydrochloride also inhibits Abl-1, DDR2, EPHA2, KDR, and RET (IC50=<0.5, 7.0, 11, 6.2, 0.8 nM). ML786 dihydrochloride can be used for the research of cancers.
-
DDR2-IN-2
0 ImagesCat. No.: HY-176849CAS No.: 3038810-93-1DDR2-IN-2 is a Discoidin domain receptor 2 (DDR2) inhibitor. DDR2-IN-2 can be used for the research of cancer.
-
DDR1-IN-8
0 ImagesCat. No.: HY-162102CAS No.: 3038810-92-0DDR1-IN-8 (compound 7s) is a potent inhibitor of DDR1/2, with the IC50 values of 0.045 μM and 0.126 μM, respectively. DDR1-IN-8 has anti-tumor activity.
-
DDR1/2 inhibitor-3
0 ImagesCat. No.: HY-122848CAS No.: 2241813-33-0DDR1/2 inhibitor-3 (5n) is a DDR1/2 inhibitor, with IC50 valuesof 9.4 and 20.4 nM, respectively. DDR1/2 inhibitor-3 can be used in anti-inflammatory research.
- 1
