DMU2139 |
رقم الكتالوجGC19416
One-Click Copy Product Info
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DMU2139 هو مثبط قوي ومحدد لـ CYP1B1 ، مع IC50s من 9 نانومتر و 795 نانومتر لـ CYP1B1 و CYP1A1 ، على التوالي
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1821143-80-9
Sample solution is provided at 25 µL, 10mM.
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DMU2139 is a potent CYP1B1 inhibitor, with an IC50 value of 9nM[1]. DMU2139 coordinates with heme and interacts with the hydrophobic residues Phe134 and Phe231 through p-p stacking since the hydrophobic naphthyl group[2]. DMU2139 has been used in combination with cisplatin to overcome the resistance mediated by CYP1B1 and make cancer cells re-sensitized to cisplatin[3].
In vivo, the combination treatment of DMU2139 (30mg/kg) and olaparib (50mg/kg), administered by intraperitoneal injection every 4 days for 24 days, significantly inhibited tumor growth in a xenograft mouse model of A2780 cells[4].
References:
[1] Horley N J, Beresford K J M, Chawla T, et al. Discovery and characterization of novel CYP1B1 inhibitors based on heterocyclic chalcones: Overcoming cisplatin resistance in CYP1B1-overexpressing lines[J]. European journal of medicinal chemistry, 2017, 129: 159-174.
[2] Raju B, Choudhary S, Narendra G, et al. Molecular modeling approaches to address drug-metabolizing enzymes (DMEs) mediated chemoresistance: a review[J]. Drug Metabolism Reviews, 2021, 53(1): 45-75.
[3] Alsubait A, Aldossary W, Rashid M, et al. CYP1B1 gene: Implications in glaucoma and cancer[J]. Journal of cancer, 2020, 11(16): 4652.
[4] Xue Y, Yin T, Yuan S, et al. CYP1B1 promotes PARPi-resistance via histone H1. 4 interaction and increased chromatin accessibility in ovarian cancer[J]. Drug Resistance Updates, 2024, 77: 101151.
| Cell experiment [1]: | |
Cell lines | HEK293 cells |
Preparation Method | The recombinant HEK293 cells expressing CYP enzymes (1×105 cells/well) were seeded in a black 96-well transparent-bottom plate with a volume of 50μl. DMU2139 was added to the wells at different concentrations (1, 2, 4, 8, 10, 20, 40, 60, 80, and 100nM) and incubated at 37°C with 8% CO2 for 30 minutes. After incubation, 5μM of the fluorescent substrate 7-ethoxythioflavinol was added to each well, 25μl per well, and the mixture was shaken before the determination of 7-ethoxythioflavinol-O-demethylase (EROD) activity. Fluorescence detection was performed using the appropriate emission wavelength (530/30nm) and excitation wavelength (590/40nm). |
Reaction Conditions | 1, 2, 4, 8, 10, 20, 40, 60, 80, and 100nM; 30min |
Applications | DMU2139 treatment inhibited the CYP1B1 activity in HEK293 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Balb/c nude mice |
Preparation Method | Balb/c nude mice were raised under standard conditions and had free access to food and water. A2780 cells in the logarithmic growth phase were prepared at a concentration of 1×108 cells/ml, and 100µl of the cell suspension was subcutaneously injected into the axilla of each nude mouse. From the second day after injection, the tumor size was measured. When the average tumor volume reached approximately 100mm3, olaparib was administered intraperitoneally at a dose of 50mg/kg every 4 days, or in combination with DMU2139 (30mg/kg; i.p.) for 24 days. Measurements were taken using a vernier caliper every four days, and the formula for calculating tumor volume was: Volume (mm3) = (length×width2)/2. |
Dosage form | 30mg/kg; every 4 days for 24 days; i.p. |
Applications | DMU2139 treatment in combination with olaparib significantly inhibited the growth of A2780 cell-xenograft tumors in mice. |
References: | |
| Cas No. | 1821143-80-9 | SDF | |
| Canonical SMILES | O=C(C1=CC=C2C=C(OC)C=CC2=C1)/C=C/C3=CC=CN=C3 | ||
| Formula | C19H15NO2 | M.Wt | 289.33 |
| الذوبان | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.4563 mL | 17.2813 mL | 34.5626 mL |
| 5 mM | 691.3 μL | 3.4563 mL | 6.9125 mL |
| 10 mM | 345.6 μL | 1.7281 mL | 3.4563 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 31 reference(s) in Google Scholar.)