| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Topoisomerase II (Top II) - pafuramidine is a prodrug that is metabolized to furamidine, which inhibits topoisomerase II. Furamidine binds to the DNA minor groove and inhibits topoisomerase II-mediated DNA relaxation, leading to DNA double-strand breaks and cell death in parasites. It also acts as a minor groove binder that interferes with transcription factor binding.
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|---|---|
| ln Vitro |
Pafuramidine maleate is an orally active prodrug of furamidine. Furamidine has potent trypanocidal activity against Trypanosoma brucei with an IC50 of 4.5 nM. It exhibits broad-spectrum antiparasitic activity against trypanosomiasis, Pneumocystis pneumonia, and malaria. It also rescues mis-splicing in myotonic dystrophy type 1 models.
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| ln Vivo |
In vivo, pafuramidine maleate has a 93% Phase 3 cure rate against Human African Trypanosomiasis. It has 50-70% oral absorption and is converted to furamidine in vivo. It has been evaluated in clinical trials for HAT and Pneumocystis pneumonia. In a DM1 mouse model, a combination of erythromycin and pafuramidine displayed both additive and synergistic mis-splicing rescue.
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| Enzyme Assay |
Topoisomerase II inhibition assays use purified recombinant topoisomerase II and supercoiled plasmid DNA as substrate. Pafuramidine (and its active metabolite furamidine) is incubated with the enzyme at increasing concentrations. DNA relaxation is assessed by agarose gel electrophoresis, and IC50 values are determined. DNA binding affinity is measured by fluorescence polarization or surface plasmon resonance using AT-rich DNA sequences.
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| Cell Assay |
Trypanosoma brucei cultures are grown in HMI-9 medium supplemented with 10% FBS at 37°C. Pafuramidine is added at various concentrations (0.1 nM-10 µM) for 24-72 hours. Parasite viability is assessed by resazurin or Alamar Blue assays. IC50 values are determined from dose-response curves. Cellular uptake and metabolism of pafuramidine to furamidine are measured by LC-MS/MS.
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| Animal Protocol |
Animal studies use mouse models of Human African Trypanosomiasis (Trypanosoma brucei infection). Pafuramidine maleate is administered orally by gavage at doses of 1-50 mg/kg/day for 5-10 days. Parasite burden in blood and tissues is assessed by microscopy or quantitative PCR. Cure rates are determined at 30-90 days post-treatment. Pharmacokinetic parameters (Cmax, AUC, half-life) are determined by LC-MS/MS.
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| References |
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| Molecular Formula |
C24H24N4O7
|
|---|---|
| Molecular Weight |
480.469965934753
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| Exact Mass |
480.164
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| CAS # |
837369-26-3
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| Related CAS # |
Pafuramidine;186953-56-0
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| PubChem CID |
11691495
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.259
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
596
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(=CC=C1C1C=CC(/C(=N/OC)/N)=CC=1)C1C=CC(/C(=N/OC)/N)=CC=1.OC(/C=C\C(=O)O)=O
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| InChi Key |
SWMNGXODFOCPKQ-BTJKTKAUSA-N
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| InChi Code |
InChI=1S/C20H20N4O3.C4H4O4/c1-25-23-19(21)15-7-3-13(4-8-15)17-11-12-18(27-17)14-5-9-16(10-6-14)20(22)24-26-2;5-3(6)1-2-4(7)8/h3-12H,1-2H3,(H2,21,23)(H2,22,24);1-2H,(H,5,6)(H,7,8)/b;2-1-
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| Chemical Name |
(Z)-but-2-enedioic acid;N'-methoxy-4-[5-[4-[(Z)-N'-methoxycarbamimidoyl]phenyl]furan-2-yl]benzenecarboximidamide
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0813 mL | 10.4065 mL | 20.8130 mL | |
| 5 mM | 0.4163 mL | 2.0813 mL | 4.1626 mL | |
| 10 mM | 0.2081 mL | 1.0406 mL | 2.0813 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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