| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
Discoidin domain receptor 1 (DDR1). DDR1-IN-7rh is a potent and selective inhibitor of DDR1 with an IC50 of 13.1 nM. It also inhibits DDR2 with an IC50 of 203 nM, and shows inhibitory activity against Bcr-Abl and c-Kit with IC50 values of 414 and 2500 nM, respectively. DDR1 is a receptor tyrosine kinase activated by collagen that plays important roles in cell adhesion, migration, and proliferation.
|
|---|---|
| ln Vitro |
7rh (compound 1) exhibits a strong inhibitory impact on DDR1 (IC50 of 13.1 nM), but its effect on DDR2 (IC50 of 203 nM) is minimal. With IC50 values of 414 and 2500 nM, respectively, 7rh demonstrates inhibitory action against both Bcr-Abl and c-Kit [1].
7rh inhibits DDR1-mediated signaling induced by soluble collagen. It inhibits activation of PYK2 and PEAK1 signaling. 7rh induces a significant decrease in total protein levels of DDR1 and Bcl-xL, and causes a significant reduction in the level of MMP-2 in NSCLC cells. The compound exhibits a strong inhibitory impact on DDR1 with an IC50 of 13.1 nM. |
| ln Vivo |
7rh has antitumor effects in nasopharyngeal carcinoma cells. As an orally available DDR1 inhibitor, it has potential for in vivo efficacy in various cancer models. The compound's ability to inhibit DDR1-mediated signaling and reduce MMP-2 levels suggests potential anti-metastatic activity. Further in vivo studies are needed to fully characterize its therapeutic potential.
|
| Enzyme Assay |
In vitro kinase inhibition assays for 7rh are performed using recombinant DDR1 kinase. The assay typically measures the phosphorylation of a peptide substrate using 33P-ATP or using fluorescence-based or luminescence-based detection methods. 7rh is incubated with the kinase, substrate, and ATP at varying concentrations, and kinase activity is quantified. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
Cellular assays for 7rh are performed using DDR1-expressing cancer cell lines, such as NSCLC or nasopharyngeal carcinoma cells. Cells are treated with 7rh at varying concentrations, and DDR1-mediated signaling is assessed by Western blot for phosphorylation of downstream targets (e.g., PYK2, PEAK1). Cell proliferation, migration, and invasion assays are performed to assess functional effects. MMP-2 levels are measured by zymography or ELISA.
|
| Animal Protocol |
In vivo animal studies for 7rh would typically be performed using mouse xenograft models of DDR1-dependent cancers. Tumor-bearing mice are administered 7rh via oral gavage at various doses. Tumor volume is monitored every 2-3 days. At study termination, tumors are analyzed for DDR1 inhibition, downstream signaling, and markers of proliferation and apoptosis. The compound's oral availability makes it suitable for such studies.
|
| ADME/Pharmacokinetics |
7rh has a molecular weight of 546.59 and molecular formula C30H29F3N6O. It is soluble in DMSO (25 mg/mL) and is practically insoluble in water and ethanol. For in vivo studies, formulations include 5% DMSO + 40% PEG300 + 5% Tween 80 + 50% ddH2O (1.25 mg/mL) or 5% DMSO + 95% corn oil (0.2 mg/mL). The compound should be stored at -20°C.
|
| Toxicity/Toxicokinetics |
Toxicological data for 7rh are limited to in vitro studies. Standard safety precautions should be followed when handling 7rh. Comprehensive toxicology studies would be required before clinical development. The compound is for research use only and is not for therapeutic use. No specific acute toxicity data have been reported in the literature.
|
| References | |
| Additional Infomation |
DDR1-IN-7rh (7rh, DDR1-IN-2) is a potent, selective, ATP-competitive, and orally available inhibitor of discoidin domain receptor 1 (DDR1). It inhibits DDR1 with an IC50 of 6.8-13.1 nM and shows selectivity over DDR2, Bcr-Abl, and c-Kit. 7rh is a click chemistry reagent containing an alkyne group. The compound has shown antitumor effects in nasopharyngeal carcinoma cells and is a valuable tool for studying DDR1 biology and validating DDR1 as a therapeutic target in cancer. 7rh is for research use only and has not been approved for clinical use.
|
| Molecular Formula |
C30H29F3N6O
|
|---|---|
| Molecular Weight |
546.59
|
| Exact Mass |
546.235
|
| CAS # |
1429617-90-2
|
| PubChem CID |
71550931
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Index of Refraction |
1.616
|
| LogP |
4.32
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
40
|
| Complexity |
925
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCC1=C(C=C(C=C1)C(=O)NC2=CC(=CC(=C2)C(F)(F)F)CN3CCN(CC3)C)C#CC4=CN5C(=CC=N5)N=C4
|
| InChi Key |
DDLPXZXBWGJRGK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C30H29F3N6O/c1-3-23-6-7-25(16-24(23)5-4-21-18-34-28-8-9-35-39(28)20-21)29(40)36-27-15-22(14-26(17-27)30(31,32)33)19-38-12-10-37(2)11-13-38/h6-9,14-18,20H,3,10-13,19H2,1-2H3,(H,36,40)
|
| Chemical Name |
4-ethyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide
|
| Synonyms |
DDR1 Inhibitor 7rh; 7RH; DDR1-IN-7rh
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~114.35 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.81 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 20.8 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: ≥ 2.08 mg/mL (3.81 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 | 1.8295 mL | 9.1476 mL | 18.2952 mL | |
| 5 mM | 0.3659 mL | 1.8295 mL | 3.6590 mL | |
| 10 mM | 0.1830 mL | 0.9148 mL | 1.8295 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
