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| Targets |
WRG-28 targets discoidin domain receptor 2 (DDR2), a collagen-activated receptor tyrosine kinase implicated in tumor progression, fibrosis, and tissue remodeling. As a selective, extracellularly acting allosteric inhibitor, WRG-28 uniquely inhibits receptor-ligand interactions through allosteric modulation of the receptor. By blocking DDR2 signaling, WRG-28 inhibits tumor invasion, migration, and the tumor-supporting effects of cancer-associated fibroblasts (CAFs). WRG-28 also shows good activity in relieving rheumatoid arthritis in the CAIA mouse model.
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| ln Vitro |
WRG-28 (1, 2 μM; 4 hours) fragments collagen I-mediated tyrosine phosphorylation of DDR2 and (1 μM; 7) ERK activation and SNAIL1 protein stability in HEK293 cells expressing DDR2 ( WRG -28 (1 μM; 48 hours) inhibits tumor cell wavelength and migration by inhibiting DDR2 in BT549 and 4T1 breast cancer cells [1]. WRG-28 (1 μM; 4). WRG-28 (0.5, 1 μM ; 4 h) Maintain varied inhibitory impact of acquired DDR2 on TKIs [1].
In vitro, WRG-28 inhibits DDR2 with an IC50 of 230 nM. The compound inhibits tumor invasion, migration, and the tumor-supporting effects of cancer-associated fibroblasts (CAFs). WRG-28 also inhibits metastatic breast tumor cell colonization in the lungs. The compound's allosteric mechanism of action provides a unique approach to targeting DDR2, distinguishing it from ATP-competitive kinase inhibitors. WRG-28 has demonstrated efficacy in inhibiting cancer cell invasion and migration in various in vitro models. |
| ln Vivo |
In breast cancers, WRG-28 (10 mg/kg; IV; single dose) internally turns off DDR2's molecular signaling [1]. The WRG-28 (10 mg/kg; iv; single dose) administered once daily for 7 days and WRG-28 (10 mg/kg; iv; administered once daily for 21 days) is used to treat arthritis-induced inflammation (CAIA) and spinal cord damage [2].
In vivo, WRG-28 (10 mg/kg; intravenous; single dose) attenuates biochemical signaling of DDR2 in breast tumors. WRG-28 (10 mg/kg; intravenous; once daily for 7 days) reduces metastatic lung colonization of breast tumor cells. WRG-28 (10 mg/kg; intravenous; once daily for 21 days) decreases both the inflammatory reaction and joint destruction in mice with collagen antibody-induced arthritis (CAIA). In tumor-bearing mice, a single 10 mg/kg intravenous dose reduced SNAIL1-CBG levels within the tumor by 60%. |
| Enzyme Assay |
Receptor binding or kinase activity assays for WRG-28 are performed using purified recombinant DDR2 kinase domain or using cell-based assays measuring DDR2 autophosphorylation. For kinase assays, DDR2 activity is measured by monitoring the phosphorylation of a peptide substrate in the presence of ATP. WRG-28 is incubated with the enzyme, substrate, and ATP at varying concentrations. The reaction is stopped, and product formation is quantified. IC50 values are calculated from concentration-response curves. Alternatively, cell-based assays measure DDR2 phosphorylation by Western blot following collagen stimulation.
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| Cell Assay |
Cell viability assay [1]
Cell Types: Day) Inhibit the tumor-promoting effect of CAF [1]. HEK293 cells (transfected with DDR2-Flag) Tested Concentrations: 0.25, 0.5, 1, 2 µM Incubation Duration: 4 hrs (hours) Experimental Results: 1 or 2 µM Dramatically inhibited collagen I-mediated DDR2 tyrosine phosphorylation, IC>sub >50 is 286 nm. Cell viability assay [1] Cell Types: HEK293 cells (transfected with DDR2-Flag) Tested Concentrations: 1 µM Incubation Duration: 7 hrs (hours) Experimental Results: Inhibition of collagen I-mediated ERK activation and SNAIL1 protein stabilization (IC50=286 nM). Cell viability assay [1] Cell Types: BT549 and 4T1 breast cancer cells (expressing endogenous DDR2) Tested Concentrations: 1 μM Incubation Duration: 48 h Experimental Results: Inhibition of DDR2-induced tumor cell invasion and migration. Cell viability assay[1] Cell Types: CAF cells (containing tumor organoids) Tested Concentrations: 1 μM Incubation Duration: 4 days Experimental Results: Inhibition of DDR2 activity that supports invasion of primary tumor organoids in CAF. Cell viability assay [1] Cell Types: HEK2 Cellular assays for WRG-28 are performed using cancer cell lines that express DDR2, such as breast cancer cell lines, or using cancer-associated fibroblasts (CAFs). Cells are cultured in appropriate media and treated with WRG-28 at varying concentrations for defined time periods. Cell invasion and migration are assessed using Boyden chamber or wound healing assays. The tumor-supporting effects of CAFs are assessed by co-culture experiments. DDR2 signaling is assessed by measuring the phosphorylation of DDR2 and downstream signaling molecules by Western blot. |
| Animal Protocol |
Animal/Disease Models: Female BALB/cJ mouse (8 weeks old; 4T1-Snail-CBG tumor-bearing mouse model) [1].
Doses: 10 mg/kg Route of Administration: intravenous (iv) (iv)injection, single dose. Experimental Results: SNAIL1-clic beetle green (SNAIL1.CBG) levels in mouse tumors were diminished by 60%. Animal/Disease Models: Female BALB/cJ mice (8 weeks old; injected with 4T1 GFP-luc expressing cells) [1]. Doses: 10 mg/kg Route of Administration: intravenous (iv) (iv)injection, one time/day for 7 days. Experimental Results: Lung colonization was diminished to levels comparable to shDDR2-depleted cells. Animal/Disease Models: Male DBA/1 mice (8 weeks old; CAIA model) [2]. Doses: 10 mg/kg Route of Administration: intravenously (iv) (iv)(iv), one time/day for 21 days. Experimental Results: The mice's arthritis Dramatically improved (the production of IL-15 and Dkk-1 was diminished), and the mice's hind paw thickness was also diminished. Inhibits inflammatory cell infiltration and cartilage destruction in mouse ankle joints and serum. Dramatically reduces bone destruction, reduces joint space enlargement and bo In vivo studies with WRG-28 are conducted in mouse models of breast cancer metastasis and collagen antibody-induced arthritis (CAIA). WRG-28 is administered via intravenous injection at doses such as 10 mg/kg. For metastasis studies, lung colonization of breast tumor cells is assessed by bioluminescence imaging or histology. For arthritis studies, inflammatory reaction and joint destruction are assessed by clinical scoring and histology. Biochemical signaling is assessed by measuring DDR2 pathway activation in tumor tissues. |
| ADME/Pharmacokinetics |
WRG-28 has a molecular weight of 410.44 and a molecular formula of C21H18N2O5S. The compound is soluble in DMSO at 15.62 mg/mL (38.06 mM). It should be stored at -20degC. The compound has a predicted boiling point of 603.4+/-65.0degC and a density of 1.38+/-0.1 g/cm3. Detailed pharmacokinetic parameters, including half-life and bioavailability, are documented in the scientific literature.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for WRG-28 are not extensively documented in publicly available sources. The compound is intended for research use only and is not approved for human therapeutic applications. In preclinical studies, WRG-28 has been administered at doses such as 10 mg/kg without reported significant adverse effects. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and adherence to institutional biosafety and chemical hygiene guidelines.
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| References |
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| Additional Infomation |
WRG-28 is a selective, extracellularly acting DDR2 allosteric inhibitor with an IC50 of 230 nM. It uniquely inhibits receptor-ligand interactions through allosteric modulation of the receptor. WRG-28 inhibits tumor invasion, migration, and the tumor-supporting effects of cancer-associated fibroblasts (CAFs). It also inhibits metastatic breast tumor cell colonization in the lungs and shows activity in relieving rheumatoid arthritis in the CAIA mouse model. WRG-28 is for research purposes only.
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| Molecular Formula |
C21H18N2O5S
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| Molecular Weight |
410.443024158478
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| Exact Mass |
410.093
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| CAS # |
1913291-02-7
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| PubChem CID |
139035038
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| Appearance |
Pink to red solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
819
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC(=CC=1)COC1C=CC2=C(C=1)OC1=CC(C=CC1=N2)=O)(NCC)(=O)=O
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| InChi Key |
AARVTLIQNGAELZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H18N2O5S/c1-2-22-29(25,26)17-7-3-14(4-8-17)13-27-16-6-10-19-21(12-16)28-20-11-15(24)5-9-18(20)23-19/h3-12,22H,2,13H2,1H3
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| Chemical Name |
N-ethyl-4-[(7-oxophenoxazin-3-yl)oxymethyl]benzenesulfonamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~15.62 mg/mL (~38.06 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.56 mg/mL (3.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.6 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4364 mL | 12.1820 mL | 24.3641 mL | |
| 5 mM | 0.4873 mL | 2.4364 mL | 4.8728 mL | |
| 10 mM | 0.2436 mL | 1.2182 mL | 2.4364 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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