EFAPROXIRAL SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H22NO4.Na
Molecular Weight	363.3827
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CC1=CC(NC(=O)CC2=CC=C(OC(C)(C)C([O-])=O)C=C2)=CC(C)=C1

InChI

InChIKey=SWDPIHPGORBMFR-UHFFFAOYSA-M

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15869322 | http://www.fda.gov/ohrms/dockets/ac/04/briefing/4037B1_03_Allos-RSR13.htm#_Toc68333919
Curator's Comment: Description was created based on several sources, including: http://adisinsight.springer.com/drugs/800008565

Efaproxiral is a synthetic, small molecule, radiation-sensitising agent being developed by Allos Therapeutics primarily for the treatment of cancer. It works by binding and allosterically stabilising deoxyhaemoglobin in hypoxic regions of tumour tissue. This increases oxygen uptake of the tumour tissue and restores its sensitivity to radiation therapy, making therapy potentially more successful. But no benefit was seen for efaproxiral in phase III clinical trials. The only serious adverse effect detected was hypoxaemia. 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 haemoglobin.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hemoglobin HbA 4 Target ID: CHEMBL2095168 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15869322 \| http://www.fda.gov/ohrms/dockets/ac/04/briefing/4037B1_03_Allos-RSR13.htm#_Toc68333919	Modulator 828

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT00004202	Primary	Phase II 1132	Unknown Approved Use Unknown
Glioblastoma multiforme 30 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12118029	Primary	Phase II 1132	Unknown Approved Use Unknown
Ischemic heart disease 7 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9535987	Primary	Preclinical	Unknown Approved Use Unknown
Breast cancer metastases 2 Sources: https://clinicaltrials.gov/ct2/show/NCT00083304 http://www.fda.gov/ohrms/dockets/ac/04/briefing/4037B1_03_Allos-RSR13.htm#_Toc68333919	Primary	Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
RSR13, a potential athletic performance enhancement agent: detection in urine by gas chromatography/mass spectrometry.	2001	11746905
Allosteric modification of oxygen delivery by hemoglobin.	2001 Mar	11226087
High-resolution crystal structure of deoxy hemoglobin complexed with a potent allosteric effector.	2001 May	11316875
The effect of RSR13, a synthetic allosteric modifier of hemoglobin, on brain tissue pO2 (measured by EPR oximetry) following severe hemorrhagic shock in rats.	2003	14562728
The dose-dependent effect of RSR13, a synthetic allosteric modifier of hemoglobin, on physiological parameters and brain tissue oxygenation in rats.	2003	14562725
Novel radiosensitizers for tumors of the central nervous system.	2004 Dec	15648950
Effects of RSR13 and oxygen on the cytotoxicity of cisplatin and carboplatin to EMT6 mouse mammary tumor cells in vitro and in vivo.	2004 Jan	14574460
Effect of RSR13, an allosteric hemoglobin modifier, on oxygenation in murine tumors: an in vivo electron paramagnetic resonance oximetry and bold MRI study.	2004 Jul 1	15183487
Increased oxygenation of intracranial tumors by efaproxyn (efaproxiral), an allosteric hemoglobin modifier: In vivo EPR oximetry study.	2005 Apr 1	15817356
Efaproxiral: a radiation enhancer used in brain metastases from breast cancer.	2005 Dec	16249270
Cerebral metastases--a therapeutic update.	2006 Aug	16932601
Radiation sensitization with redox modulators: a promising approach.	2006 Feb 1	16414370
Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases.	2006 Jan 1	16314619
Efaproxiral: should we hold our breath?	2006 Jan 1	16314614
Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors.	2006 Jun 27	16800900
Mass spectrometric characterization of efaproxiral (RSR13) and its implementation into doping controls using liquid chromatography-atmospheric pressure ionization-tandem mass spectrometry.	2006 Mar	16421876
The effects of Efaproxyn (efaproxiral) on subcutaneous RIF-1 tumor oxygenation and enhancement of radiotherapy-mediated inhibition of tumor growth in mice.	2007 Aug	17638413
Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases.	2007 Dec	18091051
Role of palliative radiotherapy in brain metastases.	2009 Jan	20606860
Whole brain radiotherapy with radiosensitizer for brain metastases.	2009 Jan 6	19126230

Patents

Sample Use Guides

In Vivo Use Guide

Efaproxiral was administered intravenously via a central venous access device over 30 minutes; the infusion was completed no more than 30 minutes before whole-brain radiation therapy. The intended daily dose of efaproxiral was 75 or 100 mg/kg.

Route of Administration: Intravenous

In Vitro Use Guide

EMT6 cells in exponentially growing cell cultures were treated with 300 mg/ml of RSR13 (Efaproxiral), with radiation, or with RSR13 (Efaproxiral) plus irradiation under either aerobic or hypoxic conditions (7.5 Gy for aerobic cultures and 20 Gy for hypoxic cultures). The survival of irradiated EMT6 cells was the same whether cells were irradiated in the presence or in the absence of RSR13 (Efaproxiral).

Name

Type

Language

EFAPROXIRAL SODIUM

Official Name

English

RSR13 SODIUM

Code

English

2-[4-[2-[(3,5-Dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methylpropanoic acid monosodium salt

Common Name

English

EFAPROXIRAL SODIUM [USAN]

Common Name

English

2-(4-(((3,5-DIMETHYLANILINO)CARBONYL)METHYL)-PHENOXY)-2-METHYLPROPIONIC ACID SODIUM

Systematic Name

English

EFAPROXIRAL SODIUM [MART.]

Common Name

English

RSR-13 SODIUM

Code

English

PROPANOIC ACID, 2-(4-(2-((3,5-DIMETHYLPHENYL)AMINO)-2-OXOETHYL)PHENOXY)-2-METHYL-, MONOSODIUM SALT

Common Name

English

Efaproxiral sodium [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C798