Efaproxiral

Title: Efaproxiral
CAS Registry Number: 131179-95-8
CAS Name: 2-[4-[2-[(3,5-Dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methylpropanoic acid
Additional Names: 2-4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxy-2-methylpropionic acid
Manufacturers' Codes: RSR-13
Molecular Formula: C20H23NO4
Molecular Weight: 341.40
Percent Composition: C 70.36%, H 6.79%, N 4.10%, O 18.75%
Literature References: Allosteric modifier of hemoglobin (Hb). Binds in the central water cavity of the Hb molecule causing a conformational change such that bound oxygen is released more readily. Prepd not claimed: D. J. Abraham et al., US 5049695 (1991 to Center Innovative Technol.); eidem., J. Med. Chem. 34, 752 (1991). Oxygen binding affinities and mechanism of action: D. J. Abraham et al., Biochemistry 31, 9141 (1992). Effect on myocardial oxygen concentration: P. S. Pagel et al., J. Pharmacol. Exp. Ther. 285, 1 (1998). Antimetastatic effects: B. A. Teicher et al., Cancer Chemother. Pharmacol. 42, 24 (1998). Clinical pharmacokinetics and pharmacodynamics: L. Kleinberg et al., J. Clin. Oncol. 17, 2593 (1999). Clinical evaluation in brain tumor therapy: eidem, ibid. 20, 3149 (2002).
Properties: mp 85°.
Melting point: mp 85°
Therap-Cat: Antineoplastic adjunct (radiosensitizer).
Keywords: Antineoplastic Adjunct; Radiosensitizer.
Efavirenz Eflornithine Efloxate Efonidipine Efrotomycin

Efaproxiral
Efaproxiral.png
Systematic (IUPAC) name
2-[4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methylpropanoic acid
Clinical data
Legal status  ?
Pharmacokinetic data
Half-life 1 hr
Identifiers
CAS number 131179-95-8 YesY
ATC code L01XD06
PubChem CID 122335
UNII J81E81G364 N
ChEMBL CHEMBL18901 N
Chemical data
Formula C20H23NO4 
Mol. mass 341.40 g/mol
 N (what is this?)  (verify)

Efaproxiral (INN) is an analog of the cholesterol drug bezafibrate developed for the treatment of depression, traumatic brain injury, ischemia, stroke, myocardial infarction, diabetes, hypoxia, sickle cell disease, hypercholesterolemia and as a radio sensitizer.[1][2][3] The chemical is a propanoic acid in the class of amphipathic carboxylic acids. Most propanoic acid produced is consumed as a preservative for both animal feed and food for human consumption. One use for efaproxiral is to increase the efficacy of certain chemotherapy drugs which have reduced efficacy against hypoxic tumours, and can thus be made more effective by increased offloading of oxygen into the tumour tissues.[4][5][6] No benefit was seen for efaproxiral in phase III clinical trials.[7] The increased oxygenation of tissues could theoretically also produce enhanced exercise capacity in feline, rat and canine models for approximately 100 min. immediately after a high dosage 45 min. intravenous infusion.[8] This has led World Anti-Doping Agency to categorize efaproxiral under a prohibited method to artificially enhance the uptake, transport or delivery of oxygen.[9] There is no existing evidence that efaproxiral can effectively enhance performance in humans.[10] Efaproxiral can be absorbed via transdermal, rectal, inhalation and gastrointestinal routes, though not at plasma concentrations great enough to alter the oxygen-haemoglobin dissociation curve.[11] Efaproxiral is explicitly excluded from the 2012 World Anti-Doping Agency list of Prohibited Substances and is explicitly included in the Prohibited Methods section M1 as a forbidden procedure to alter the oxygen-haemoglobin dissociation curve in order to allosterically modify hemoglobin. [12]