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

Molecular Formula	C20H22NO4
Molecular Weight	340.393
Charge	-1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	Na
Molecular Weight	22.98976928
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 846

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 211 Sources: https://clinicaltrials.gov/ct2/show/NCT00004202	Primary	Phase II 1147	Unknown Approved Use Unknown
Glioblastoma multiforme 30 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12118029	Primary	Phase II 1147	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 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
333 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11240256/	75 mg/kg single, intravenous dose: 75 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		EFAPROXIRAL red blood cells	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
459 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11240256/	100 mg/kg single, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		EFAPROXIRAL red blood cells	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11240256/	75 mg/kg single, intravenous dose: 75 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		EFAPROXIRAL red blood cells	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11240256/	100 mg/kg single, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		EFAPROXIRAL red blood cells	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	Disc. AE: Adult respiratory distress syndrome, Creatinine increased... Other AEs: Nausea, Headache... AEs leading to discontinuation/dose reduction: Adult respiratory distress syndrome (grade 5, 2%) Creatinine increased (grade 4, 2%) Sepsis (grade 4, 2%) Other AEs: Nausea (grade 3, 2%) Headache (grade 3, 2%) Allergic rash (grade 3, 4%) Hypoxemia (grade 3, 6%) Hypotension (grade 3, 2%) Creatinine increased (grade 3, 2%) Sepsis (grade 3, 2%) Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/

AEs

AE	Significance	Dose	Population
Creatinine increased	grade 3, 2%	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/
Headache	grade 3, 2%	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/
Hypotension	grade 3, 2%	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/
Nausea	grade 3, 2%	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/
Sepsis	grade 3, 2%	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/
Allergic rash	grade 3, 4%	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/
Hypoxemia	grade 3, 6%	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/
Creatinine increased	grade 4, 2% Disc. AE	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/
Sepsis	grade 4, 2% Disc. AE	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/
Adult respiratory distress syndrome	grade 5, 2% Disc. AE	100 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 100 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12118029/

PubMed

Title	Date	PubMed
Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study.	2010-03	19767314
The role of emerging and investigational therapies for metastatic brain tumors: a systematic review and evidence-based clinical practice guideline of selected topics.	2010-01	19957013
Whole brain radiotherapy with radiosensitizer for brain metastases.	2009-01-06	19126230
Role of palliative radiotherapy in brain metastases.	2009-01	20606860
Quality of life in brain metastases radiation trials: a literature review.	2008-10	19008990
Neuropsychological testing and biomarkers in the management of brain metastases.	2008-09-17	18798997
Reduction in hemoglobin-oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure.	2008-08-26	18718428
Trimethylaluminium mediated amide bond formation in a continuous flow microreactor as key to the synthesis of rimonabant and efaproxiral.	2008-03-07	18292903
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.	2007-12	18091051
The effects of Efaproxyn (efaproxiral) on subcutaneous RIF-1 tumor oxygenation and enhancement of radiotherapy-mediated inhibition of tumor growth in mice.	2007-08	17638413
Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems.	2007-03-26	17386108
Using exposure-response and biomarkers to streamline early drug development.	2007	17117714
Current therapeutic approaches in patients with brain metastases.	2006-11	17032560
Cerebral metastases--a therapeutic update.	2006-08	16932601
Blood doping by cobalt. Should we measure cobalt in athletes?	2006-07-24	16863591
Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors.	2006-06-27	16800900
Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases.	2006-06-19	16773073
Role of efaproxiral in metastatic brain tumors.	2006-04	16613536
Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival.	2006-03-15	16446056
Efaproxiral (RSR13) plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors.	2006-03	16514179
Mass spectrometric characterization of efaproxiral (RSR13) and its implementation into doping controls using liquid chromatography-atmospheric pressure ionization-tandem mass spectrometry.	2006-03	16421876
Radiation sensitization with redox modulators: a promising approach.	2006-02-01	16414370
New hope for old drug in patients with brain metastases.	2006-02	16468181
Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases.	2006-01-01	16314619
Efaproxiral: should we hold our breath?	2006-01-01	16314614
Efaproxiral: a radiation enhancer used in brain metastases from breast cancer.	2005-12	16249270
Phase II multicenter study of induction chemotherapy followed by concurrent efaproxiral (RSR13) and thoracic radiotherapy for patients with locally advanced non-small-cell lung cancer.	2005-09-01	16135463
Increased oxygenation of intracranial tumors by efaproxyn (efaproxiral), an allosteric hemoglobin modifier: In vivo EPR oximetry study.	2005-04-01	15817356
Hit to Lead Success Stories--IBC Conference: Effective chemistry strategies for reducing attrition rates and speeding lead compounds into the pipeline. 31 January-1 February 2005, San Diego, CA, USA.	2005-03	15772889
R-state hemoglobin bound to heterotropic effectors: models of the DPG, IHP and RSR13 binding sites.	2005-01-31	15670819
Modeling of the response of ptO2 in rat brain to changes in physiological parameters.	2005	16594142
Effects of a pharmacologically-induced shift of hemoglobin-oxygen dissociation on myocardial energetics during ischemia in patients with coronary artery disease.	2005	16136855
Efaproxiral: GSJ 61, JP 4, KDD 86, RS 4, RSR 13.	2005	15869322
Novel radiosensitizers for tumors of the central nervous system.	2004-12	15648950
Effect of RSR13, an allosteric hemoglobin modifier, on oxygenation in murine tumors: an in vivo electron paramagnetic resonance oximetry and bold MRI study.	2004-07-01	15183487
Efaproxiral: a novel radiation sensitiser.	2004-05	15155129
Effects of RSR13 and oxygen on the cytotoxicity of cisplatin and carboplatin to EMT6 mouse mammary tumor cells in vitro and in vivo.	2004-01	14574460
Efaproxiral (Allos Therapeutics).	2003-08	12917776
RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database.	2003-06-15	12805339
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
Allosteric modification of hemoglobin by RSR13 as a therapeutic strategy.	2003	14562722
[Blood doping and cardiovascular consequences].	2002-12-21	12579085
Survival of patients with newly diagnosed glioblastoma multiforme treated with RSR13 and radiotherapy: results of a phase II new approaches to brain tumor therapy CNS consortium safety and efficacy study.	2002-07-15	12118029
Increasing P(50) does not improve DO(2CRIT) or systemic VO(2) in severe anemia.	2002-07	12063279
Pharmacological correction of hypothermic P(50) shift does not alter outcome from focal cerebral ischemia in rats.	2002-05	11959653
Effects of enhanced oxygen release from hemoglobin by RSR13 in an acute renal failure model.	2001-10	11576354
Enhancement of tumor oxygenation and radiation response by the allosteric effector of hemoglobin, RSR13.	2001-09	11500138
High-resolution crystal structure of deoxy hemoglobin complexed with a potent allosteric effector.	2001-05	11316875
RSR13, a potential athletic performance enhancement agent: detection in urine by gas chromatography/mass spectrometry.	2001	11746905

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).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:04:23 GMT 2025` Edited by `admin` on `Mon Mar 31 18:04:23 GMT 2025`
Record UNII	3L83QP52XI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RSR-13 SODIUM

Preferred Name

English

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

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