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Revision as of 04:56, 28 September 2010 editحسن علي البط (talk | contribs)Extended confirmed users, Pending changes reviewers19,940 editsm Adding category Category:Phenol ethers (using HotCat)← Previous edit		Latest revision as of 10:44, 28 June 2024 edit undoAnil1956 (talk | contribs)Extended confirmed users2,198 editsNo edit summary
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			{{short description|Chemical compound}}
	{{Drugbox		{{Drugbox
			| Verifiedfields = changed
⚫	| IUPAC_name = 2--2-oxoethyl]phenoxy]-2-methylpropanoic acid
			| Watchedfields = changed
⚫	| image = Efaproxiral.png
			| verifiedrevid = 387464773
⚫	| CAS_number = 131179-95-8
		⚫	| IUPAC_name = 2--2-oxoethyl]phenoxy]-2-methylpropanoic acid
	| CAS_supplemental =
		⚫	| image = Efaproxiral.png
⚫	| ATC_prefix = L01
⚫	| ATC_suffix = XD06
			<!--Clinical data-->
⚫	| ATC_supplemental =
			| tradename =
⚫	| PubChem = 122335
	| DrugBank =		| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
		⚫	| pregnancy_US = <!-- A / B / C / D / X -->
⚫	| chemical_formula =
		⚫	| pregnancy_category =
		⚫	| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
		⚫	| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
		⚫	| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
		⚫	| legal_status =
		⚫	| routes_of_administration =
			<!--Pharmacokinetic data-->
		⚫	| bioavailability =
		⚫	| protein_bound =
		⚫	| elimination_half-life = 1 hr
		⚫	| excretion =
			<!--Identifiers-->
			| CAS_number_Ref = {{cascite|correct|??}}
		⚫	| CAS_number = 131179-95-8
		⚫	| ATC_prefix = L01
		⚫	| ATC_suffix = XD06
		⚫	| ATC_supplemental =
		⚫	| PubChem = 122335
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank =
			| UNII_Ref = {{fdacite|changed|FDA}}
			| UNII = J81E81G364
			| ChEMBL_Ref = {{ebicite|changed|EBI}}
			| ChEMBL = 18901
			| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
			| ChemSpiderID = 109085
			<!--Chemical data-->
		⚫	| chemical_formula =
	| C=20 | H=23 | N=1 | O=4		| C=20 | H=23 | N=1 | O=4
		⚫	| smiles = Cc1cc(cc(c1)NC(=O)Cc2ccc(cc2)OC(C)(C)C(=O)O)C
	| molecular_weight = 341.40 g/mol
			| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
⚫	| smiles = CC1=CC(=CC(=C1)NC(=O)CC2=CC=C(C=C2)OC(C)(C)C(=O)O)C
			| StdInChI = 1S/C20H23NO4/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)
⚫	| bioavailability =
			| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
⚫	| protein_bound =
	| digestion =		| StdInChIKey = BNFRJXLZYUTIII-UHFFFAOYSA-N
⚫	| elimination_half-life =
⚫	| excretion =
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
⚫	| pregnancy_US = <!-- A / B / C / D / X -->
⚫	| pregnancy_category=
⚫	| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
⚫	| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
	| legal_AS = <!-- GSL, P, POM, CD, or Class A, B, C -->
⚫	| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
⚫	| legal_status =
⚫	| routes_of_administration =
	}}		}}
			'''Efaproxiral''' (]) is an analogue of ] , developed for the treatment of ], ], ischemia, stroke, myocardial infarction, ], hypoxia, sickle cell disease, ] and as a radio sensitiser.<ref>{{cite book | vauthors = Farace E, Melikyan Z |chapter= Cognitive Dysfunction, Mood Disorders, and Fatigue | title = Cancer Neurology in Clinical Practice |year=2008 |pages=242–248 |doi= 10.1007/978-1-59745-412-4_7 |isbn=978-1-58829-983-3 }}</ref><ref>{{Cite patent | country = US | number = 5731454| url=http://www.freepatentsonline.com/5731454.html | title=Allosteric modifiers of hemoglobin useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored blood | inventor = Abraham DJ, Joshi G, Randad R, Panikker J | assign1 = Virginia Commonwealth University (Richmond, VA) | gdate = 24 March 1998 | postscript = . }}</ref><ref name="pmid8770102">{{cite journal | vauthors = Kunert MP, Liard JF, Abraham DJ | title = RSR-13, an allosteric effector of hemoglobin, increases systemic and iliac vascular resistance in rats | journal = The American Journal of Physiology | volume = 271 | issue = 2 Pt 2 | pages = H602–H613 | date = August 1996 | pmid = 8770102 | doi = 10.1152/ajpheart.1996.271.2.H602 }}</ref>
	'''Efaproxiral''' (]) is an allosteric effector of ].<ref name="pmid8770102">{{cite journal |author=Kunert MP, Liard JF, Abraham DJ |title=RSR-13, an allosteric effector of hemoglobin, increases systemic and iliac vascular resistance in rats |journal=Am. J. Physiol. |volume=271 |issue=2 Pt 2 |pages=H602–13 |year=1996 |month=August |pmid=8770102 |doi= |url=http://ajpheart.physiology.org/cgi/pmidlookup?view=long&pmid=8770102}}</ref> It increases the oxygen-carrying capacity of hemoglobin, and is normally used to increase the efficacy of certain ] drugs which have reduced efficacy against ] (oxygen-poor) tumours, and can thus be made more effective by increasing oxygenation of the tumour tissues.<ref>{{cite journal |author=Donnelly ET, Liu Y, Rockwell S |title=Efaproxiral (RSR13) plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors |journal=Exp. Biol. Med. (Maywood) |volume=231 |issue=3 |pages=317–21 |year=2006 |month=March |pmid=16514179 |url=http://www.ebmonline.org/cgi/pmidlookup?view=long&pmid=16514179}}</ref><ref>{{cite journal |author=Engel RH, Kaklamani VG |title=Role of efaproxiral in metastatic brain tumors |journal=Expert Rev Anticancer Ther |volume=6 |issue=4 |pages=477–85 |year=2006 |month=April |pmid=16613536 |doi=10.1586/14737140.6.4.477 |url=http://www.future-drugs.com/doi/abs/10.1586/14737140.6.4.477?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov}}</ref><ref>{{cite journal |author=Scott C, Suh J, Stea B, Nabid A, Hackman J |title=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 |journal=Am. J. Clin. Oncol. |volume=30 |issue=6 |pages=580–7 |year=2007 |month=December |pmid=18091051 |doi=10.1097/COC.0b013e3180653c0d |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0277-3732&volume=30&issue=6&spage=580}}</ref> However this increased oxygenation of tissues can also produced enhanced exercise capacity,<ref>{{cite journal |author=Watanabe T, Takeda T, Omiya S, ''et al.'' |title=Reduction in hemoglobin-oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure |journal=J. Am. Coll. Cardiol. |volume=52 |issue=9 |pages=779–86 |year=2008 |month=August |pmid=18718428 |doi=10.1016/j.jacc.2008.06.003 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(08)01988-8}}</ref> which has led to efaproxiral being added to the ] banned list for athletes in competition.<ref></ref>
			The chemical is a ] of ]. One use for efaproxiral is to increase the efficacy of certain ] drugs which have reduced efficacy against ] tumours, and can thus be made more effective by increased offloading of oxygen into the tumour tissues.<ref>{{cite journal | vauthors = Donnelly ET, Liu Y, Rockwell S | title = Efaproxiral (RSR13) plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors | journal = Experimental Biology and Medicine | volume = 231 | issue = 3 | pages = 317–321 | date = March 2006 | pmid = 16514179 | doi = 10.1177/153537020623100312 | s2cid = 19475480 }}</ref><ref>{{cite journal | vauthors = Engel RH, Kaklamani VG | title = Role of efaproxiral in metastatic brain tumors | journal = Expert Review of Anticancer Therapy | volume = 6 | issue = 4 | pages = 477–485 | date = April 2006 | pmid = 16613536 | doi = 10.1586/14737140.6.4.477 | s2cid = 3142753 }}</ref><ref>{{cite journal | vauthors = Scott C, Suh J, Stea B, Nabid A, Hackman J | title = 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 | journal = American Journal of Clinical Oncology | volume = 30 | issue = 6 | pages = 580–587 | date = December 2007 | pmid = 18091051 | doi = 10.1097/COC.0b013e3180653c0d | s2cid = 42750048 }}</ref> No benefit was seen for efaproxiral in phase III clinical trials.<ref>{{Cite web | url=https://www.drugs.com/nda/rsr13_040504.html | title=FDA Advisory Committee Does Not Recommend Approval of RSR13 as Adjunctive Therapy for the Treatment of Brain Metastases Originating from Breast Cancer | date = May 2004 | via = Drugs.com | work = Allos Therapeutics, Inc. }}</ref> 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.<ref>{{cite journal | vauthors = Watanabe T, Takeda T, Omiya S, Hikoso S, Yamaguchi O, Nakano Y, Higuchi Y, Nakai A, Abe Y, Aki-Jin Y, Taniike M, Mizote I, Matsumura Y, Shimizu T, Nishida K, Imai K, Hori M, Shirasawa T, Otsu K | display-authors = 6 | title = Reduction in hemoglobin-oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure | journal = Journal of the American College of Cardiology | volume = 52 | issue = 9 | pages = 779–786 | date = August 2008 | pmid = 18718428 | doi = 10.1016/j.jacc.2008.06.003 | name-list-style = vanc | doi-access = free }}</ref>
⚫	==References==
⚫	{{Reflist}}
			This has led ] to categorise efaproxiral under a prohibited method to artificially enhance the uptake, transport or delivery of oxygen.<ref>{{cite web | url = http://www.wada-ama.org/rtecontent/document/2009_Prohibited_List_ENG_Final_20_Sept_08.pdf | work = World Anti Dopting Agency (WADA) | title = The 2009 Prohibited List | date = 24 August 2011 | archive-url = https://web.archive.org/web/20090203030039/http://www.wada-ama.org/rtecontent/document/2009_Prohibited_List_ENG_Final_20_Sept_08.pdf | archive-date=2009-02-03 }}</ref> There is no existing evidence that efaproxiral can effectively enhance performance in humans.<ref>{{cite journal | vauthors = Nóbrega AC |title=RSR13 e modificação alostérica da afinidade hemoglobina-oxigênio: abuso entre atletas|trans-title=RSR13 and allosteric change in the hemoglobin-oxygen {{sic|nolink=y|reason=error in source|Afinity}} |journal=Journal of Sports Medicine|volume=8 |date=Feb 2002 |pages=26–29 |doi=10.1590/S1517-86922002000100005 |issn= 1517-8692 |url=http://www.scielo.br/scielo.php?pid=S1517-86922002000100005&script=sci_arttext|language=pt}}</ref> Efaproxiral can be absorbed via transdermal, rectal, inhalation and gastrointestinal routes, though not at plasma concentrations great enough to alter the ].<ref>{{cite book | vauthors = Campanini B, Raboni M |chapter=Oxygen Delivery by Allosteric Effectors of Hemoglobin, Blood Substitutes, and Plasma Expanders |title=Burger's Medicinal Chemistry, Drug Discovery and Development |date=January 2003 |pages=385–441 |doi= 10.1002/0471266949.bmc048 |isbn=978-0471266945 }}</ref>
			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 ] in order to allosterically modify haemoglobin.<ref>{{cite web |url=http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/2012/WADA_Prohibited_List_2012_EN.pdf |title = The Prohibited List 2012 | work = World Anti Dopting Agency (WADA) | date = 24 August 2011 |access-date=2012-05-10 |url-status=dead |archive-url=https://web.archive.org/web/20120513020202/http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/2012/WADA_Prohibited_List_2012_EN.pdf |archive-date=2012-05-13 }}</ref>
⚫	{{Chemotherapeutic agents}}
		⚫	== References ==
		⚫	{{Reflist}}
		⚫	{{Chemotherapeutic agents}}
	]		]
	]		]
	]		]
			]
	{{antineoplastic-drug-stub}}