| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
DDR1 29 nM (IC50) DDR2 1900 nM (IC50)
DDR1-IN-4 targets Discoidin Domain Receptor 1 (DDR1), a receptor tyrosine kinase activated by collagen. Overactivation of DDR1 is implicated in cancer progression, fibrosis, and inflammatory diseases. By blocking DDR1 signaling, it disrupts tumor cell proliferation, epithelial–mesenchymal transition, and pathological extracellular matrix remodeling. Its selectivity for DDR1 over DDR2 is a key feature. |
|---|---|
| ln Vitro |
In HT1080 cells overexpressing DDR1, DDR1-IN-4 (Compound 2.45) exhibits a definite dose-dependent inhibition of DDR1 phosphorylation, with more than 70% of phosphorylation inhibition at a concentration of 1 μM and selectivity over inhibition of DDR2[1].
In vitro, DDR1-IN-4 has been shown to be a potent inhibitor of DDR1 autophosphorylation with an IC50 of 29 nM. It also inhibits DDR2, but with significantly lower potency (IC50 of 1.9 μM). This selectivity profile makes it a valuable tool for studying DDR1-specific signaling pathways. |
| ln Vivo |
Using DDR1-IN-4 (Compound 2.45, ip, 90 mg/kg) at a therapeutic dose preserves renal function and minimizes tissue damage in Col4a3–/– mice (the preclinical animal model of Alport syndrome), demonstrating the true therapeutic benefit of specifically suppressing DDR1 phosphorylation in vivo[1].
In vivo activity of DDR1-IN-4 has been studied in animal models of cancer, fibrosis, and inflammatory diseases. By blocking DDR1 signaling, it disrupts tumor cell proliferation and pathological extracellular matrix remodeling. These studies provide evidence for its therapeutic potential in various disease conditions. |
| Enzyme Assay |
Cell-free assays for DDR1-IN-4 typically involve measuring its inhibitory activity against DDR1 and DDR2 kinases using biochemical kinase assays. The IC50 values of 29 nM and 1.9 μM for DDR1 and DDR2, respectively, are determined by measuring the phosphorylation of a peptide substrate in the presence of varying concentrations of the inhibitor.
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| Cell Assay |
In vitro cellular assays are conducted to evaluate the functional activity of DDR1-IN-4. Cancer cell lines and fibrotic models are treated with the compound. DDR1 phosphorylation is measured to assess the inhibition of collagen-induced signaling. Cell proliferation, migration, and extracellular matrix remodeling are measured to evaluate the compound's effects.
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| Animal Protocol |
Animal/Disease Models: Col4a3–/– mice, a mouse model phenocopying Alport syndrome[1].
Doses: 90 mg/kg. Route of Administration: Injected intraperitoneally (ip) daily. Experimental Results: Resulted in a significant reduction of fibrosis evaluated by Picro Sirius Red, smooth muscle actin staining, and collagen I accumulation. Dramatically reduces the levels of pDDR1 in Col4a3 knockout mice compared to controls. In vivo animal experiments typically involve xenograft models of cancer or models of fibrosis and inflammation. Animals are administered DDR1-IN-4. Tumor growth, fibrosis, or inflammation is monitored over time to assess the compound's efficacy. These studies are essential for demonstrating the in vivo activity of the compound. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of DDR1-IN-4 are typical of a small molecule inhibitor. Its molecular weight is 565.34. While detailed PK parameters are not widely published, its properties suggest it is designed to have favorable drug-like characteristics, including good permeability and metabolic stability, to support efficacy in vivo.
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| Toxicity/Toxicokinetics |
The toxicity profile of DDR1-IN-4 is not extensively documented but is likely to be similar to other kinase inhibitors. Common adverse effects may include fatigue and gastrointestinal disturbances. Preclinical studies would typically involve acute and chronic dosing in animal models to assess safety margins.
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| References | |
| Additional Infomation |
DDR1-IN-4 is a research compound used to study DDR1-driven pathways in cancer, fibrosis, and inflammatory diseases. Its potency and selectivity make it a valuable tool for preclinical drug discovery and mechanistic studies. The compound is not approved for therapeutic use and is intended for research purposes only.
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| Molecular Formula |
C23H20BRF3N6O3
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|---|---|
| Molecular Weight |
565.342514038086
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| Exact Mass |
564.073
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| CAS # |
2125676-13-1
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| PubChem CID |
130301864
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
36
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| Complexity |
884
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1=CC=CC2=C1C1(C(N2CC(NCC(F)(F)F)=O)=O)CCN(C(C2C=CC3=C(C=NN3)N=2)=O)CC1
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| InChi Key |
UXEXYURPAPXPSR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H20BrF3N6O3/c24-13-2-1-3-17-19(13)22(21(36)33(17)11-18(34)28-12-23(25,26)27)6-8-32(9-7-22)20(35)15-5-4-14-16(30-15)10-29-31-14/h1-5,10H,6-9,11-12H2,(H,28,34)(H,29,31)
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| Chemical Name |
2-[4-bromo-2-oxo-1'-(1H-pyrazolo[4,3-b]pyridine-5-carbonyl)spiro[indole-3,4'-piperidine]-1-yl]-N-(2,2,2-trifluoroethyl)acetamide
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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: 250 mg/mL (442.21 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7688 mL | 8.8442 mL | 17.6885 mL | |
| 5 mM | 0.3538 mL | 1.7688 mL | 3.5377 mL | |
| 10 mM | 0.1769 mL | 0.8844 mL | 1.7688 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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