| Size | Price | Stock | Qty |
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| 500mg |
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| 1g |
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Purity: ≥98%
Dicoumarol (also named as Dicumarol) is an oral and competitive inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1) and PDK1 with IC50s of 0.37 and 19.42 μM, respectively. It works as an anticoagulant by obstructing vitamin K metabolism. Dicoumarol is a naturally occurring anticoagulant that works similarly to warfarin, a medication that dicoumarol inspired, in that it depletes vitamin K. It also functions as a reductase inhibitor in biochemical experiments. It depletes the amount of active vitamin K in the blood because, like all 4-hydroxycoumarin drugs, it is a competitive inhibitor of the enzyme vitamin K epoxide reductase, which recycles vitamin K.
| Targets |
NQO1 (IC50 = 0.37 μM); PDK1 (IC50 = 19.42 μM)
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| ln Vitro |
Dicoumarol is used as a control for PDK1 and NAD (P) H:quinone oxidoreductase 1 (NQO1), having IC50 values of 19.42±0.032 μM and 0.37±0.15, respectively. Dicoumarol is designed to prevent the action of PDK1. Upon exposure to 200 μM dicoumarol, PDK1's enzymatic activity was almost 94% decreased. Dicoumarol decreased the levels of p-PDHA1 by 26% at 100 μM and 72% at 200 μM, whereas there was no significant change in the overall levels of PDHA1. Dicoumarol at concentrations of 100 and 200 μM both strongly induced. Similarly, treatment with 100 μM and 200 μM dicoumarol produced approximately 20.87% and 24.94%, respectively, according to flow cytometry examination of annexin V+PI+ cells. grafted cells, most particularly after undergoing multiple solvent treatments [2]. Additionally, it was noted that MCF-7-TAMR cells' tamoxifen-responsive phenotype was reversed when they were treated with the well-known NQO1 dicoumarol [3].
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| ln Vivo |
Tumor weight and volume were considerably decreased as compared to tumors from the solvent or desert groups when dichloroacetate (DCA) at 100 mg/kg, dicoumarol at 30 mg/kg, and dicoumarol at 50 mg/kg were administered. When SKOV3 xenografts treated with dicoumarol were compared to tumors in the vehicle or vehicle groups, there was a significant decrease in total caspase-3 and total anti-poly(ADP-ribose) polymerase (PARP) [2].
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| Cell Assay |
The in vitro cell viability is examined using the standard MTT assay. In 96-well plates, 8000 SKOV3 or A2780 cells are seeded per well. The following day, each well is filled with Dicoumarol (DIC) in escalating concentrations, and the plate is incubated for 24 hours. The plate is then incubated for an additional 4 hours before each well is filled with 10 μL of 10 mg/mL MTT reagent in phosphate-buffered saline (PBS). After shaking the plate for 5 minutes, the reader measures the optical density at 570 nm after the formazan crystals have been dissolved in 150 μL of DMSO[2].
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| Animal Protocol |
We use twenty-five female BALB/c-nu mice that are 15 g in weight and 5 to 6 weeks old. The upper flank is subcutaneously injected with a total of 1 107 SKOV3 cells. The nude mice are randomized into five groups (n=5/group) after 10 days, when the tumor volume reaches roughly 100 mm3, and are treated intraperitoneally (i.p.) every other day for a total of 12 days with the following medications: Dichloroacetate (DCA) group received 100 mg/kg of DCA; Dicoumarol (DIC)-30 group received 30 mg/kg of Dicoumarol; and Dicoumarol-50 group received 50 mg/kg of Dicoumarol. Control groups received 0.2 mL of 0.9% NaCl, 1 mM NaOH, and Dichloroacetate (DCA) group received 100 mg/kg of DCA. Every other day until sacrifice (day 12 following the initial treatment), the body weights and tumor volumes of each mouse are measured[2].
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| References |
[1]. Bian J, et al. Affinity-based small fluorescent probe for NAD(P)H:quinone oxidoreductase 1 (NQO1). Design, synthesis and pharmacological evaluation. Eur J Med Chem. 2017 Feb 15;127:828-839.
[2]. Zhang W, et al. Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells. PLoS One. 2017 Jun 15;12(6):e0179672. [3]. Fiorillo M, et al. Mitochondrial "power" drives tamoxifen resistance: NQO1 and GCLC are new therapeutic targets in breast cancer. Oncotarget. 2017 Mar 2;8(12):20309-20327 |
| Molecular Formula |
C19H12O6
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| Molecular Weight |
336.29
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| Exact Mass |
336.06339
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| Elemental Analysis |
C, 67.86; H, 3.60; O, 28.55
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| CAS # |
66-76-2
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
C1=CC=C2C(=C1)C(=C(C(=O)O2)CC3=C(C4=CC=CC=C4OC3=O)O)O
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| InChi Key |
DOBMPNYZJYQDGZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H12O6/c20-16-10-5-1-3-7-14(10)24-18(22)12(16)9-13-17(21)11-6-2-4-8-15(11)25-19(13)23/h1-8,20-21H,9H2
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| Chemical Name |
4-hydroxy-3-[(4-hydroxy-2-oxochromen-3-yl)methyl]chromen-2-one
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| Synonyms |
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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 |
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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: ≥ 1.67 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 16.7 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9736 mL | 14.8681 mL | 29.7362 mL | |
| 5 mM | 0.5947 mL | 2.9736 mL | 5.9472 mL | |
| 10 mM | 0.2974 mL | 1.4868 mL | 2.9736 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04741334 | Completed | Drug: Dicumarols |
Cerebral Hemorrhage Craniocerebral Trauma |
Fondazione Policlinico Universitario Agostino Gemelli IRCCS |
September 27, 2019 |
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