| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
Purity: ≥98%
| Targets |
Efaproxiral targets hemoglobin (Hb), the oxygen-carrying protein in red blood cells. It binds in the central water cavity of the Hb molecule, causing a conformational change such that bound oxygen is released more readily. This allosteric modification reduces Hb-oxygen binding affinity. By increasing oxygen release to tissues, efaproxiral enhances oxygenation of hypoxic tumors.
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| ln Vitro |
In the central water cavity of Hb, efaproxiral only binds to two symmetrically linked locations [2]. When serum albumin solution is present, epsilon easily passes through the red blood cell membrane [2]. In the presence of anion channel blockers (DIDS), efaproxiral entry into red blood cells is not impeded [2].
In vitro, efaproxiral (100 μM) enhances radiation-induced cytotoxicity. It reduces the oxygen binding affinity of hemoglobin in isolated human whole blood. The compound's ability to increase P50 and enhance oxygen release has been characterized in vitro. These activities support its use as a radiation sensitizer. |
| ln Vivo |
Efaproxiral (150 mg/kg, intraperitoneal injection) can enhance tumor oxygenation and boost the inhibitory effect of radiation on tumor growth within 5 days of treatment [3]. Efaproxiral lowers hemoglobin-oxygen binding affinity, stimulates hemoglobin to release oxygen to adjacent tissues, and may increase tumor pO(2)[4]
In vivo, efaproxiral increases oxygenation of intracranial tumors. It enhances radiation therapy by improving tumor oxygenation. Efaproxiral increases the tumor growth inhibition of radiotherapy over 5 days of treatment. It has been investigated as a radiation sensitizer for the treatment of brain tumors. |
| Enzyme Assay |
In vitro hemoglobin oxygen dissociation assays for efaproxiral measure the oxygen binding affinity of hemoglobin. Whole blood or purified hemoglobin is incubated with various concentrations of efaproxiral. Oxygen dissociation curves are generated using a hemoximeter or similar instrument. P50 values (partial pressure of oxygen at 50% saturation) are calculated. Increased P50 indicates reduced oxygen affinity.
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| Cell Assay |
Cellular assays for efaproxiral use cancer cell lines. Cells are treated with various concentrations of efaproxiral, with or without radiation. Cell viability is measured using clonogenic assays or MTT assays. Radiation-induced cytotoxicity is assessed. These assays confirm the compound's radiosensitizing activity.
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| Animal Protocol |
Animal/Disease Models: Female C3H/HEJ mice (18-20 g), radiation-induced fibrosarcoma tumors ( RIF-1) cell xenograft [3]
Doses: 150 mg/kg Route of Administration: intraperitoneal (ip) injection; prior to X-ray irradiation (4 Gy/day) for 5 days Experimental Results: Significant increase in tumor oxygenation over 5 days 8.4 to 43.4 mmHg, with the greatest increase occurring 22-31 minutes after treatment. In vivo animal studies for efaproxiral utilize tumor models, such as intracranial tumor models. The compound is administered intravenously or intraperitoneally. Radiation is co-administered. Tumor oxygenation is measured by EPR oximetry. Tumor volume is measured over time. Efficacy is compared to radiation alone. Pharmacokinetic sampling is performed. |
| ADME/Pharmacokinetics |
Efaproxiral has molecular weight of 341.40 g/mol and molecular formula C20H23NO4. It is a synthetic small molecule. It is typically stored at -20°C. It is soluble in DMSO. Pharmacokinetic properties include good oral bioavailability. The compound binds to hemoglobin and distributes to tissues. It is metabolized in the liver and excreted renally.
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| Toxicity/Toxicokinetics |
Preclinical toxicity of efaproxiral has been evaluated in standard toxicology studies. As a hemoglobin modifier, potential adverse effects may include cardiovascular effects due to altered oxygen delivery. No significant toxicity has been reported at therapeutic doses. The compound is for research use only and is not approved for clinical use in most regions.
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| References |
[1]. Stea B, et al. Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases. Br J Cancer. 2006 Jun 19;94(12):1777-1784.
[2]. Abraham DJ, et al. Allosteric modifiers of hemoglobin: 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl]phenoxy]-2-methylpropionic acid derivatives that lower the oxygen affinity of hemoglobin in red cell suspensions, in whole blood, and in vivo in rats. [3]. Hou H, et al. The effects of Efaproxyn (efaproxiral) on subcutaneous RIF-1 tumor oxygenation and enhancement of radiotherapy-mediated inhibition of tumor growth in mice. Radiat Res. 2007 Aug;168(2):218-25. [4]. Hou H, et al. Increased oxygenation of intracranial tumors by efaproxyn (efaproxiral), an allosteric hemoglobin modifier: In vivo EPR oximetry study. Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1503-9. |
| Additional Infomation |
Efeprola is a small synthetic molecule with radiosensitizing activity. Efeprola increases oxygen content in hypoxic tumor tissue by non-covalently binding to hemoglobin tetramer, thereby reducing the affinity of hemoglobin for oxygen. Increased tumor oxygenation can reduce tumor radioresistance. (NCI04)
See also: Efeprola sodium (note moved to). Efaproxiral (RSR13) is a synthetic allosteric modifier of hemoglobin. It reduces Hb-oxygen binding affinity and facilitates oxygen release. It has been investigated as a radiation sensitizer for brain tumors. It is available for research purposes only. |
| Molecular Formula |
C20H23NO4
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|---|---|
| Molecular Weight |
341.4
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| Exact Mass |
341.163
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| CAS # |
131179-95-8
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| Related CAS # |
Efaproxiral sodium;170787-99-2;Efaproxiral-d6;1246815-16-6
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| PubChem CID |
122335
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| Appearance |
White to off-white solid powder
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| Density |
1.202g/cm3
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| Boiling Point |
554.5ºC at 760mmHg
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| Flash Point |
289.2ºC
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| Vapour Pressure |
3.93E-13mmHg at 25°C
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| Index of Refraction |
1.597
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| LogP |
3.799
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
458
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(OC1=CC=C(CC(NC2=CC(C)=CC(C)=C2)=O)C=C1)C(O)=O
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| InChi Key |
BNFRJXLZYUTIII-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H23NO4/c1-13-9-14(2)11-16(10-13)21-18(22)12-15-5-7-17(8-6-15)25-20(3,4)19(23)24/h5-11H,12H2,1-4H3,(H,21,22)(H,23,24)
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| Chemical Name |
2-[4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methylpropanoic acid.
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| Synonyms |
RSR13 RSR-13 RSR 13 NSC-722758 NSC722758 NSC 722758 Efaproxyn
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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) |
DMSO : ≥ 150 mg/mL (~439.37 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.09 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 (6.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 27.5 mg/mL (80.55 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9291 mL | 14.6456 mL | 29.2912 mL | |
| 5 mM | 0.5858 mL | 2.9291 mL | 5.8582 mL | |
| 10 mM | 0.2929 mL | 1.4646 mL | 2.9291 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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