Efaproxiral Sodium (RSR13) is a synthetic allosteric modifier of hemoglobin (Hb) and a bezafibrate analog used for brain metastases originating from breast cancer. Efaproxiral has been shown to bind reversibly to hemoglobin, stabilizing the deoxyhemoglobin tetramer conformation to reduce its affinity for oxygen. Efaproxiral plus oxygen breathing reduces the radiobiological hypoxic fraction of EMT6 tumors from the value of 24% found in both air-breathing and oxygen-breathing mice to 9% and improves the response of the tumors to radiation. It also has the potential to be used for the treatment of depression, traumatic brain injury, ischemia, stroke, myocardial infarction, diabetes, hypoxia, sickle cell disease, hypercholesterolemia and as a radio sensitiser.

Physicochemical Properties

Molecular Formula	C20H22NNAO4
Molecular Weight	363.3828
Exact Mass	363.144
CAS #	170787-99-2
Related CAS #	Efaproxiral;131179-95-8
PubChem CID	2725048
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	6
Heavy Atom Count	26
Complexity	464
Defined Atom Stereocenter Count	0
InChi Key	SWDPIHPGORBMFR-UHFFFAOYSA-M
InChi Code	InChI=1S/C20H23NO4.Na/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);/q;+1/p-1
Chemical Name	Sodium 2-[4-[2-[(3,5-Dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methylpropanoate
Synonyms	RSR 13sodium; RSR-13; RSR13
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In vitro activity: Efaproxiral, a synthetic allosteric modifier of hemoglobinoxygen binding affinity, has been shown to bind reversibly to hemoglobin, stabilizing the deoxyhemoglobin tetramer conformation to reduce its affinity for oxygen.
ln Vivo	Efaproxiral plus oxygen breathing reduces the radiobiological hypoxic fraction of EMT6 tumors from the value of 24% found in both air-breathing and oxygen-breathing mice to 9% and improves the response of the tumors to radiation. Carboplatin (100 mg/kg) slowes tumor growth in air-breathing mice, producing a growth delay of 3.3 days. Efaproxiral plus oxygen increases the growth delay to 5.7 days; this is 2.4 days (71%) greater than that for carboplatin alone and 2.1 days (57%) greater than that for carboplatin plus oxygen breathing. Efaproxiral plus oxygen breathing, therefore, improves the tumor growth delay obtained with 100 mg/kg carboplatin to or beyond that obtained with the highly toxic dose of 150 mg/kg carboplatin, but does so without increasing the toxicity beyond that seen with 100 mg/kg carboplatin in air-breathing mice. Efaproxiral significantly increases tumor oxygenation by 8.4 to 43.4 mmHg within 5 days in C3H mice with RIF-1 tumors, with maximum increases at 22-31 min after treatment. Efaproxiral plus oxygen plus Radiation produces tumor growth inhibition throughout the treatment duration in C3H mice with RIF-1 tumors, and inhibition is significantly different from radiation plus oxygen from day 3 to day 5.
Animal Protocol	Mice
References	Exp Biol Med (Maywood).2006 Mar;231(3):317-21;Radiat Res.2007 Aug;168(2):218-25.
Additional Infomation	Efaproxiral Sodium is the sodium salt form of efaproxiral, a propanoic acid and allosteric modifier of hemoglobin, with radiosensitizing activity. Efaproxiral binds non-covalently to the hemoglobin tetramer, thereby decreasing hemoglobin-oxygen binding affinity. This results in an increase in oxygen levels in hypoxic tumor tissues; increasing tumor oxygenation reduces tumor radioresistance.

Solubility Data

Solubility (In Vitro)

DMSO:73 mg/mL (200.9 mM) Water:73 mg/mL (200.9 mM) Ethanol:73 mg/mL (200.9 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.72 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 (5.72 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7519 mL	13.7597 mL	27.5194 mL
	5 mM	0.5504 mL	2.7519 mL	5.5039 mL
	10 mM	0.2752 mL	1.3760 mL	2.7519 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.