![Ethanone,1-[4-[2-hydroxy-3-(5-quinolinyloxy)propyl]-1-piperazinyl]-2,2-diphenyl-](/upload/0290/3dd64c0b-b713-460b-95b6-70a3ff1b8442.png)
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| 10mg |
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| Targets |
The compound is a P-glycoprotein (P-gp) inhibitor. It reverses P-gp-mediated MDR by inhibiting the efflux pump activity of P-gp, thereby increasing intracellular accumulation of chemotherapeutic drugs. It is a quinoline compound.
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| ln Vitro |
Dofequidar completely reverses resistance against vincristine in vitro in multidrug-resistant variants of mouse leukemia P388 cells and human leukemia K562 cells at 1-10 μM. The compound inhibits P-gp-mediated drug efflux, restoring sensitivity to chemotherapy drugs in resistant cancer cells.
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| ln Vivo |
In vivo, Dofequidar is an orally active P-gp inhibitor. It has been studied for its ability to reverse multidrug resistance and enhance the efficacy of chemotherapy in animal models and clinical trials. The compound's oral bioavailability makes it suitable for combination therapy with anticancer drugs.
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| Enzyme Assay |
In vitro assays for P-gp inhibition typically use membrane vesicles or cell lines overexpressing P-gp. The compound's ability to inhibit P-gp-mediated transport of a fluorescent substrate (e.g., rhodamine 123, calcein-AM) is measured. Cells are incubated with the substrate and increasing concentrations of the compound. Fluorescence accumulation is measured by flow cytometry or fluorometry. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell-based multidrug resistance reversal assays use P-gp-overexpressing cancer cell lines (e.g., P388/ADR, K562/ADR). Cells are treated with a chemotherapy drug (e.g., vincristine, doxorubicin) in the presence and absence of Dofequidar. Cell viability is assessed after 48-72 hours. The compound's ability to restore drug sensitivity is quantified by the fold reversal of resistance. Combination index analysis is performed to determine synergistic effects.
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| Animal Protocol |
In vivo animal studies for Dofequidar typically involve administering the compound to mice bearing P-gp-overexpressing tumor xenografts. The compound is given orally in combination with a chemotherapy drug. Tumor growth inhibition is monitored. Pharmacokinetic studies assess the compound's ability to increase drug accumulation in tumors. Survival is also assessed. The compound's efficacy in reversing MDR in vivo is evaluated.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Dofequidar are characteristic of orally active small molecules. The compound is orally bioavailable. Following administration, it is absorbed and distributed to tissues, including tumors. It inhibits P-gp in target tissues, increasing the accumulation of co-administered drugs. Metabolism occurs primarily in the liver via CYP450 enzymes. Excretion occurs through biliary and renal pathways.
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| Toxicity/Toxicokinetics |
Toxicological profile of Dofequidar is consistent with P-gp inhibitors. Common side effects include gastrointestinal disturbances, headache, and dizziness. The compound may also affect the pharmacokinetics of other drugs by inhibiting P-gp in the gut and liver. Drug-drug interactions are a concern. The compound has been evaluated in clinical trials and shown to be generally well-tolerated.
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| References |
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| Additional Infomation |
Dofequidar is an anti-tumor drug. It is an orally administered synthetic quinoline derivative with multidrug resistance modulating properties. Dofequidar binds to the drug-binding site of the transmembrane P-glycoprotein efflux pump, preferentially transporting it out of the cell and thus blocking the efflux of other therapeutic drugs.
Dofequidar (MS-209) is a quinoline compound that was developed as a P-gp inhibitor to reverse multidrug resistance in cancer chemotherapy. It was investigated in clinical trials for various cancers, including breast cancer and lung cancer. The compound's development was discontinued, but it remains a valuable research tool for studying P-gp-mediated MDR. |
| Molecular Formula |
C30H31N3O3
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| Molecular Weight |
481.58544
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| Exact Mass |
481.237
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| CAS # |
129716-58-1
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| PubChem CID |
213040
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| Density |
1.228g/cm3
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| Boiling Point |
720.8ºC at 760mmHg
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| Flash Point |
389.7ºC
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| Vapour Pressure |
8.36E-22mmHg at 25°C
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| Index of Refraction |
1.64
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| LogP |
3.826
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
36
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| Complexity |
652
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(COC1=C2C=CC=NC2=CC=C1)CN3CCN(C(C(C4=CC=CC=C4)C5=CC=CC=C5)=O)CC3
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| InChi Key |
KLWUUPVJTLHYIM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H31N3O3/c34-25(22-36-28-15-7-14-27-26(28)13-8-16-31-27)21-32-17-19-33(20-18-32)30(35)29(23-9-3-1-4-10-23)24-11-5-2-6-12-24/h1-16,25,29,34H,17-22H2
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| Chemical Name |
1-[4-(2-hydroxy-3-quinolin-5-yloxypropyl)piperazin-1-yl]-2,2-diphenylethanone
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0765 mL | 10.3823 mL | 20.7646 mL | |
| 5 mM | 0.4153 mL | 2.0765 mL | 4.1529 mL | |
| 10 mM | 0.2076 mL | 1.0382 mL | 2.0765 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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