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Purity: ≥98%
DDR1-IN-1 is a potent and selective discoidin domain receptor 1 (DDR1) receptor tyrosine kinase inhibitor with IC50 of 105 nM, and is about 3-fold selectivity over DDR2. As measured against a panel of 451 kinases, DDR1-IN-1 binds to DDR1 in the conformation known as "DFG-out" and, at submicromolar concentrations, inhibits DDR1 autophosphorylation in cells with good selectivity. A helpful pharmacological probe for DDR1-dependent signal transduction is provided by DDR1-IN-1. Matrix collagens trigger the activation of the DDR1 receptor tyrosine kinase, which is involved in many cellular processes including adhesion, invasion, migration, and proliferation.
| Targets |
DDR1 (IC50 = 105 nM); DDR2 (IC50 = 413 nM)
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| ln Vitro |
DDR1-IN-1 inhibits DDR1 autophosphorylation in U2OS cells at a concentration of 86 nM, which is the basal level. The inhibition of DDR1 autophosphorylation is stronger when collagen stimulation is not present. DDR1-IN-1 does not inhibit proliferation below a concentration of 10 μM in a panel of various cancer cell lines with DDR1 gain-of-function mutations and/or overexpression, whereas GSK2126458 enhances the antiproliferative activity of DDR1-IN-1.[1]
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| Enzyme Assay |
DDR1 is brought on 48 hours before DDR1 activation by rat tail collagen I by 2 Gg/ml doxycycline. The EC50 test media containing 10 Gg/ml collagen and each concentration of the compound is used to treat the DDR1 over-expressed U2OS after the media has been pre-treated for one hour with each concentration of the compound. The lysis buffer (50 mM Tris, pH 7.5, 1% Triton X-100, 0.1% SDS, 150 mM NaCl, 5 mM EDTA, 100 mM NaF, 2 mM Na3VO4, 1 mM PMSF, 10 Gg/ml aprotinin, and 10 Gg/ml leupeptin) is used to lyse each cell after it has been rinsed three times with cold PBS. In order to calculate the EC50 after Western blotting with anti-activated human DDR1b (Y513), the activation of DDR1 is measured by density using the ImageJ program.
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| Cell Assay |
In 96-well plates, cells are plated in triplicate at a density of 3000 cells per well; in 384-well plates, the same density is applied. For 48 hours, different concentrations of compounds are added to plates. CellTiter-Glo and CCK-8 are used to measure cell viability. Both assays are carried out in compliance with the manufacturer's guidelines. Luminescence for the CellTiter-Glo assay is measured using a multi-label reader. Absorbance for the CCK-8 assay is measured at 450 nm in a microplate reader. The data are presented as the mean of at least two independent measurements with a standard error of less than 20%, normalized to the control group (DMSO). Prism 5.0 was used to calculate GI50.
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| References | |
| Additional Infomation |
DDR1-IN-1 is a secondary carboxamide resulting from the formal condensation of the carboxy group of 4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzoic acid with the amino group of 5-(5-amino-2-methylphenoxy)-1,3-dihydro-2H-indol-2-one. It is a potent inhibitor of discoidin domain receptor tyrosine kinase 1 and 2 (DDR1/2) with IC50 = 105 nM and 413 nM, respectively. It has a role as an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor. It is a N-alkylpiperazine, a member of benzamides, a member of (trifluoromethyl)benzenes, a secondary carboxamide, an aromatic ether and a member of oxindoles.
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| Molecular Formula |
C30H31F3N4O3
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| Molecular Weight |
552.59
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| Exact Mass |
552.234
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| Elemental Analysis |
C, 65.21; H, 5.65; F, 10.31; N, 10.14; O, 8.69
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| CAS # |
1449685-96-4
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| Related CAS # |
DDR1-IN-1 dihydrochloride;1780303-76-5
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| PubChem CID |
72836888
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
609.0±55.0 °C at 760 mmHg
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| Flash Point |
322.1±31.5 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.602
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| LogP |
4.7
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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 |
7
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| Heavy Atom Count |
40
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| Complexity |
881
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1C([H])=C(C(N([H])C2C([H])=C([H])C(C([H])([H])[H])=C(C=2[H])OC2C([H])=C([H])C3=C(C=2[H])C([H])([H])C(N3[H])=O)=O)C([H])=C([H])C=1C([H])([H])N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C1([H])[H])(F)F
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| InChi Key |
AOZPVMOOEJAZGK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H31F3N4O3/c1-3-36-10-12-37(13-11-36)18-21-6-5-20(15-25(21)30(31,32)33)29(39)34-23-7-4-19(2)27(17-23)40-24-8-9-26-22(14-24)16-28(38)35-26/h4-9,14-15,17H,3,10-13,16,18H2,1-2H3,(H,34,39)(H,35,38)
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| Chemical Name |
4-[(4-ethylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(2-oxo-1,3-dihydroindol-5-yl)oxy]phenyl]-3-(trifluoromethyl)benzamide
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| Synonyms |
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| HS Tariff Code |
2934.99.03.00
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 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. Solubility in Formulation 2: 2.5 mg/mL (4.52 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8097 mL | 9.0483 mL | 18.0966 mL | |
| 5 mM | 0.3619 mL | 1.8097 mL | 3.6193 mL | |
| 10 mM | 0.1810 mL | 0.9048 mL | 1.8097 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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