関: deferoxamine、deferoxamine mesilate、Desferal

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/24 12:26:44」(JST)

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Deferoxamine (also known as desferrioxamine B, desferoxamine B, DFO-B, DFOA, DFB or desferal) is a bacterial siderophore produced by the Actinobacteria Streptomyces pilosus. It has medical applications as a chelating agent used to remove excess iron from the body.^[1] The mesylate salt of DFO-B is commercially available.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.^[2]

Medical uses

Deferoxamine is used to treat acute iron poisoning, especially in small children. This agent is also frequently used to treat hemochromatosis, a disease of iron accumulation that can be either genetic or acquired. Acquired hemochromatosis is common in patients with certain types of chronic anemia (e.g. thalassemia and myelodysplastic syndrome) who require many blood transfusions, which can greatly increase the amount of iron in the body. Administration for chronic conditions is generally accomplished by subcutaneous injection over a period of 8–12 hours each day. Administration of deferoxamine after acute intoxication may color the urine a pinkish red, a phenomenon termed "vin rosé urine".

Apart from iron toxicity, deferoxamine can be used to treat aluminium toxicity (an excess of aluminium in the body) in select patients. In US, the drug is not FDA-approved for this use.

Deferoxamine is also used to minimize doxorubicin's cardiotoxic side effects and in the treatment of a patient with aceruloplasminemia.^[3]

Mechanism

Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in the urine. By removing excess iron, the agent reduces the damage done to various organs and tissues, such as the liver. Also, it speeds healing of nerve damage (and minimizes the extent of recent nerve trauma).^{[citation needed]} Deferoxamine may modulate expression^[4] and release of inflammatory mediators by specific cell types.^[5]

Research

Deferoxamine is being studied as a treatment for spinal cord injury^[6] and intracerebral hemorrhage.^[7]

References

^ Miller, Marvin J. (1989-11-01). "Syntheses and therapeutic potential of hydroxamic acid based siderophores and analogs". Chemical Reviews 89 (7): 1563–1579. doi:10.1021/cr00097a011.
^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
^ Miyajima, H.; Takahashi, Y.; Kamata, T.; Shimizu, H.; Sakai, N.; Gitlin, J. D. : Use of desferrioxamine in the treatment of aceruloplasminemia. Ann. Neurol. 41: 404-407, 1997. PMID 9066364
^ Lee HJ, Lee J, Lee SK, Lee SK, Kim EC. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. BMC Cancer. 2007 Sep 13;7:176. PMID 17850672
^ Choi EY, Kim EC, Oh HM, Kim S, Lee HJ, Cho EY, Yoon KH, Kim EA, Han WC, Choi SC, Hwang JY, Park C, Oh BS, Kim Y, Kimm KC, Park KI, Chung HT, Jun CD. Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways. J Immunol. 2004 Jun 1;172(11):7069-77. PMID 15153529
^ http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2009/11/human_orphan_000120.jsp&mid=WC0b01ac058001d12b
^ Wu H, Wu T, Xu X, Wang J, Wang J. (May 2011). "Iron toxicity in mice with collagenase-induced intracerebral hemorrhage". J Cereb Blood Flow Metab. 31 (5): 1243–50. doi:10.1038/jcbfm.2010.209. PMC 3099628. PMID 21102602.

British National Formulary 55, March 2008; ISBN 978 085369 776 3 p. 32

UpToDate Contents

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1. サラセミアおよびその他の鉄過剰状態に対するキレート療法 chelation therapy for thalassemia and other iron overload states
2. 急性鉄中毒 acute iron poisoning
3. 慢性腎臓病におけるアルミニウム毒性 aluminum toxicity in chronic kidney disease
4. 鎌状赤血球症における赤血球輸血 red blood cell transfusion in sickle cell disease
5. βサラセミアの治療 treatment of beta thalassemia

English Journal

Prevention of degradation of the natural high potency sweetener (2R,4R)-monatin in mock beverage solutions.

Storkey C1, Pattison DI1, Koehler JA2, Gaspard DS2, Evans JC2, Hagestuen ED2, Davies MJ3.
Food chemistry.Food Chem.2015 Apr 15;173:645-51. doi: 10.1016/j.foodchem.2014.10.054. Epub 2014 Oct 18.
Exposure of the naturally-occurring sweetener monatin to light and metal ions results in loss of both parent monatin and total indole (monatin plus monatin lactone/lactam) in mock beverage solutions, with an accompanying decrease in sweetness. In this study potential protective strategies to prevent
PMID 25466071

Acute course of deferoxamine promoted neuronal differentiation of neural progenitor cells through suppression of Wnt/β-catenin pathway: A novel efficient protocol for neuronal differentiation.

Ziaei A1, Ardakani MR1, Hashemi MS1, Peymani M1, Ghaedi K2, Baharvand H3, Nasr-Esfahani MH4.
Neuroscience letters.Neurosci Lett.2015 Mar 17;590:138-44. doi: 10.1016/j.neulet.2015.01.083. Epub 2015 Feb 4.
Neural progenitor cells (NPCs) are feasible therapeutically model cells in regenerative medicine. However, a number of obstacles oppose their applications including insufficiency in differentiation protocols. These complications should be overwhelmed to obtain a significant clinical application. Def
PMID 25660235

Reduction of Oxidative Damage and Inflammatory Response in the Diaphragm Muscle of mdx Mice Using Iron Chelator Deferoxamine.

Moraes LH1, de Burgos RR, Macedo AB, de Almeida Hermes T, de Faria FM, Minatel E.
Biological trace element research.Biol Trace Elem Res.2015 Mar 13. [Epub ahead of print]
Oxidative stress and inflammatory processes strongly contribute to pathogenesis in Duchenne muscular dystrophy (DMD). Based on evidence that excess iron may increase oxidative stress and contribute to the inflammatory response, we investigated whether deferoxamine (DFX), a potent iron chelating agen
PMID 25762099

Japanese Journal

Desferrioxamine, An Iron Chelator, Induces CXCL8 Expression in U373MG Human Astrocytoma Cells

弘前医学 66(2-4), 127-134, 2016-03-25
NAID 120005728506

鉄過剰による造血障害 : その分子病態を考える

血液内科 69(2), 297-302, 2014-08
NAID 40020181944

Divergent effects of desferrioxamine on bacterial growth and characteristics

Journal of antibiotics 66(4), 199-203, 2013-04-25
NAID 10031168679

「deferoxamine mesilate」

Deferoxamine
Names
	IUPAC name N'-{5-[Acetyl(hydroxy)amino]pentyl}-N-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoyl}amino)pentyl]-N-hydroxysuccinamide
	Other names N'-[5-(Acetyl-hydroxy-amino)pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl) propanoylamino]pentyl]-N-hydroxy-butane diamide
Identifiers
CAS Registry Number	70-51-9
ATC code	V03AC01
Beilstein Reference	2514118
ChEBI	CHEBI:4356
ChEMBL	ChEMBL556
ChemSpider	2867
DrugBank	DB00746
	InChI InChI=1S/C25H48N6O8/c1-21(32)29(37)18-9-3-6-16-27-22(33)12-14-25(36)31(39)20-10-4-7-17-28-23(34)11-13-24(35)30(38)19-8-2-5-15-26/h37-39H,2-20,26H2,1H3,(H,27,33)(H,28,34) ; Key: UBQYURCVBFRUQT-UHFFFAOYSA-N ;
Jmol-3D images	Image; Image
KEGG	D03670
PubChem	2973
	SMILES Cc(:[o]):n(:[oH])CCCCC[nH]:c(:[o])CCc(:[o]):n(:[oH])CCCCC[nH]:c(:[o])CCc(:[o]):n(:[oH])CCCCCN ; CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN ;
UNII	J06Y7MXW4D
Properties
Chemical formula	C25H48N6O8
Molar mass	560.69 g·mol−1
log P	−0.614
Acidity (pKa)	9.079
Basicity (pKb)	4.918
Pharmacology
Routes of; administration	Intramuscular; Intraperitoneal; Intravenous; Oral; Subcutaneous;
	Pharmacokinetics:
Biological half-life	6 hours
Related compounds
Related alkanamides	Stearamidopropyl dimethylamine
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	Infobox references