DDR2 antibody (Gold)
- Known as:
- DDR2 (anti-) (Gold)
- Catalog number:
- orb124093
- Product Quantity:
- 100 ul
- Category:
- -
- Supplier:
- Biorb
- Gene target:
- DDR2 antibody (Gold)
Related genes to: DDR2 antibody (Gold)
- Gene:
- DDR2 NIH gene
- Name:
- discoidin domain receptor tyrosine kinase 2
- Previous symbol:
- TYRO10, NTRKR3
- Synonyms:
- TKT
- Chromosome:
- 1q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-06-17
- Date modifiied:
- 2016-10-05
Related products to: DDR2 antibody (Gold)
Related articles to: DDR2 antibody (Gold)
- Owing to its involvement in extracellular matrix-glial cell interactions, discoidin domain receptor 2 (DDR2) has emerged as a promising pharmacological target in various human diseases, including cancers and neurodegenerative disorders. Two allosteric inhibitors, WRG-28 and DDR2-IN-1, selectively target DDR2. Their therapeutic efficacy is likely to depend on blood-brain barrier (BBB) penetration; however, a lack of analytical methods has so far left their pharmacokinetic properties and BBB permeability profiles largely unexplored. In this study, a liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of WRG-28 and DDR2-IN-1 in plasma and brain tissue. The extraction procedure was simple and based on protein precipitation followed by lipid removal. This analytical method met the acceptance criteria of the European Medicines Agency guidelines. The calibration range was linear from 1 to 1000 ng/mL for both compounds. In addition, five prediction software tools were used to estimate pharmacokinetic parameters relevant to the BBB penetration of the two compounds. Finally, the method was applied in preclinical pharmacokinetic studies using elacridar, an efflux transporter inhibitor. - Source: PubMed
Publication date: 2026/06/24
Gueroue PaulBurban AudreySharanek AhmadBougueon GuillaumeBouchet StéphaneDucint DominiqueMolimard MathieuDjabarouti SarahGuyon Joris - Precise measurements of small molecule-protein interactions are critical for drug discovery. However, most biochemical profiling platforms measure binding using recombinant kinase domains or proteins in cell lysates, which can miss conformational regulation present in intact living cells. Here, we used flow cytometry-based fluorescent probe cellular binding assays (FPCBA) to demonstrate that the anticancer drug dasatinib binds native, untagged ABL1 kinase with 3-6-fold higher affinity than NanoLuc- or mVenus-tagged constructs in living cells. We further used this method for in-cell profiling of 25 native kinases, revealing conformational regulatory mechanisms, including SRC autoinhibition and membrane-dependent conformational states of DDR1, DDR2, and EPHA4 that are absent or attenuated in biochemical assays. For these studies, coumarin-dasatinib probes spanning a range of fluorophore acidity (p 4.1-7.3) were optimized for intracellular target engagement. To enhance sensitivity of detection, we found that uptake of acidic probes can be promoted by expression of the organic anion transporter OATP1B3. Quantitative flow cytometry with NIST-standardized beads established that intracellular concentrations of an intermediate-acidity 6FC-dasatinib probe approximated extracellular concentrations in HEK293T cells at equilibrium. Cellular values of dasatinib and imatinib for 25 kinases by FPCBA were broadly concordant with kinobead LC/MS measurements in cancer cell lysates but diverged substantially from recombinant KINOMEscan values, with divergences attributable to competition with ATP, autoinhibition, and membrane-dependent conformational states in living cells. FPCBA enables profiling of native protein-small molecule interactions in a physiologically relevant cellular context. - Source: PubMed
Publication date: 2026/06/23
Cool Lillian MPawar JogendraSonam SonamKumari SmitaZhao Serena LiHu XiaojunLin ZhihongWu MengHu ShuiyingPeterson Blake R - Orofacial clefting (OFC) is among the most common birth defects and can occur either as part of a syndrome or in isolation (nonsyndromic, ns). Cleft palate only (CPO) is an OFC subtype. Here, we searched for novel nsCPO risk genes carrying homozygous and compound-heterozygous variants, by analyzing exome data from six sibling pairs with nsCPO born to unaffected parents. After stringent quality control and filtering, we identified 6 homozygous variants and 32 compound-heterozygous variants in 5 and 16 candidate genes, respectively. We prioritized DDR2, a collagen-activated receptor-tyrosine-kinase influencing extracellular matrix composition, as our top candidate for functional follow-up, since variants in this gene can cause Warburg-Cinotti syndrome, the phenotypic spectrum of which includes palatal abnormalities. Knock-down and knock-out of DDR2-orthologs in zebrafish caused craniofacial abnormalities resembling CPO in humans. Zebrafish immunostaining indicated that DDR2-orthologs were expressed in mature head muscle cells, while murine single-cell RNA-Sequencing data detected Ddr2 expression only in head muscle progenitor cells; the latter finding was confirmed in human embryo sections stained for DDR2. DDR2-expressing head muscle progenitor cells may influence extracellular matrix composition through DDR2-mediated signaling, thereby affecting outgrowth, elevation, and fusion of the palatal shelves, a previously postulated mechanism involved in palatogenesis. Most established OFC genes (e.g. CDH1, CTNND1, IRF6, and GRHL3) act via mechanisms related to epithelial integrity and periderm differentiation, whereas our data provide evidence supporting DDR2 as a risk gene for nsOFC that functions by influencing extracellular matrix composition. - Source: PubMed
Capecki Julia AShkuro HelenaYilmaz ÖznurSchmitt LisaChannab KhadijaLindenberg Tobias TKruse TeresaAchterrath SarahCrespo BertaSiewert AnnaBakhshi MostafaPantel LeandraLudwig Kerstin UGeyer MatthiasMangold ElisabethOdermatt BenjaminIshorst Nina - Cardiac calcification is an age-associated pathological process that contributes to cardiac dysfunction, arrhythmia, and sudden cardiac death, yet its underlying mechanisms remain unclear. Cardiac fibroblasts (CFs) have emerged as key mediators of ectopic calcification through osteogenic differentiation. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism, has been implicated in cardiovascular pathology beyond its canonical role, but its involvement in cardiac calcification is unknown. In this study, aged mice exhibited cardiac dysfunction, interstitial fibrosis, and myocardial calcium deposition, accompanied by upregulation of osteogenic markers, including Runx2, OCN, and Osx. PCSK9 expression was increased in aged hearts and enriched in DDR2-positive cells. In vitro, senescent CFs displayed enhanced osteogenic differentiation, characterized by increased calcium deposition, alkaline phosphatase activity, and elevated expression of osteogenic markers. Recombinant PCSK9 promoted osteogenic differentiation in young CFs, whereas genetic deletion of PCSK9 attenuated these effects in senescent CFs. Pharmacological experiments suggest that PCSK9-mediated osteogenic differentiation is associated with activation of the ATF4 pathway and upregulation of Runx2 expression. These findings support a role for the PCSK9-ATF4-Runx2 signaling axis in osteogenic differentiation of CFs, providing new insights into age‑related cardiac calcification and identifying this pathway as a hypothesis‑generating candidate for future investigation. - Source: PubMed
Publication date: 2026/06/19
Liu GangCai QiuyaYe LinPan BinbinYe ChenjiZhang ShuhongSun YongkunCui ChaochuLu ChengbiaoWang Xianwei - Human induced pluripotent stem cell (hiPSC) technologies offer human-relevant cardiac models for biomedical applications. However, workflows for differentiation of cardiac stromal cells and fabrication of engineered heart tissue (EHT) commonly rely on animal serum, contrary to growing policy demands to reduce use of these products. Applying marker analysis via COL-I, DDR2 and GATA4 for cardiac fibroblasts or CD31, CD34 and CD144 for endothelial cells, we tailored Panexin, a defined serum substitute, to support high efficiency differentiation of cardiac stromal lineages to 85% purity without additional purification steps. We evaluated fabrication of EHTs using hiPSC-cardiomyocytes only (monoculture) or further combined with cardiac fibroblasts and endothelial cells (triculture; 70%:15%:15%, respectively). Panexin poorly supported fabrication and contractility of EHTs, a finding unaltered by modulating spontaneous cardiac myofibroblast activation via TGFβ inhibition. In contrast, human serum enabled fabrication of mono- and tri-culture EHTs, wherein constructs made without TGFβ signalling inhibition delivered the strongest contractile forces and exceeded comparator tissues engineered using animal serum. Our data show that iterative evaluation of serum substitutes, human serum, cell combinations and signalling pathway modulators can mitigate use of animal serum for functional EHT generation, aligning with the UK government's roadmap for alternative methods. - Source: PubMed
Publication date: 2026/06/16
Vo Nguyen T NChung KelvinNasir AishahPavlovic DavorDenning Chris