Chemistry:Efaproxiral
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| Elimination half-life | 1 hr |
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| Formula | C20H23NO4 |
| Molar mass | 341.407 g·mol−1 |
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Efaproxiral (INN) is an analogue 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 sensitiser.[1][2][3]
The chemical is a derivative of propanoic acid. 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 categorise 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 haemoglobin.[12]
References
- ↑ "Cognitive Dysfunction, Mood Disorders, and Fatigue". Cancer Neurology in Clinical Practice. 2008. pp. 242–248. doi:10.1007/978-1-59745-412-4_7. ISBN 978-1-58829-983-3.
- ↑ Abraham DJ, Joshi G, Randad R, Panikker J, "Allosteric modifiers of hemoglobin useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored blood", US patent 5731454, issued 24 March 1998, assigned to Virginia Commonwealth University (Richmond, VA).
- ↑ "RSR-13, an allosteric effector of hemoglobin, increases systemic and iliac vascular resistance in rats". The American Journal of Physiology 271 (2 Pt 2): H602–H613. August 1996. doi:10.1152/ajpheart.1996.271.2.H602. PMID 8770102.
- ↑ "Efaproxiral (RSR13) plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors". Experimental Biology and Medicine 231 (3): 317–321. March 2006. doi:10.1177/153537020623100312. PMID 16514179.
- ↑ "Role of efaproxiral in metastatic brain tumors". Expert Review of Anticancer Therapy 6 (4): 477–485. April 2006. doi:10.1586/14737140.6.4.477. PMID 16613536.
- ↑ "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". American Journal of Clinical Oncology 30 (6): 580–587. December 2007. doi:10.1097/COC.0b013e3180653c0d. PMID 18091051.
- ↑ "FDA Advisory Committee Does Not Recommend Approval of RSR13 as Adjunctive Therapy for the Treatment of Brain Metastases Originating from Breast Cancer". Allos Therapeutics, Inc.. May 2004. https://www.drugs.com/nda/rsr13_040504.html.
- ↑ "Reduction in hemoglobin-oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure". Journal of the American College of Cardiology 52 (9): 779–786. August 2008. doi:10.1016/j.jacc.2008.06.003. PMID 18718428.
- ↑ "The 2009 Prohibited List". World Anti Dopting Agency (WADA). 24 August 2011. http://www.wada-ama.org/rtecontent/document/2009_Prohibited_List_ENG_Final_20_Sept_08.pdf.
- ↑ "RSR13 e modificação alostérica da afinidade hemoglobina-oxigênio: abuso entre atletas" (in pt). Journal of Sports Medicine 8. Feb 2002. ISSN 1517-8692. http://www.scielo.br/scielo.php?pid=S1517-86922002000100005&script=sci_arttext.
- ↑ "Oxygen Delivery by Allosteric Effectors of Hemoglobin, Blood Substitutes, and Plasma Expanders". Burger's Medicinal Chemistry, Drug Discovery and Development. January 2003. pp. 385–441. doi:10.1002/0471266949.bmc048. ISBN 978-0471266945.
- ↑ "The Prohibited List 2012". World Anti Dopting Agency (WADA). 24 August 2011. http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/2012/WADA_Prohibited_List_2012_EN.pdf.
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