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Deferoxamine mesylate

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/05 10:47:34」(JST)

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Deferoxamine
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 number	70-51-9 Y
PubChem	2973
ChemSpider	2867 Y
UNII	J06Y7MXW4D Y
DrugBank	DB00746
KEGG	D03670 Y
ChEBI	CHEBI:4356 Y
ChEMBL	CHEMBL556 Y
ATC code	V03AC01
Beilstein Reference	2514118
Jmol-3D images	Image 1 Image 2
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
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) Y Key: UBQYURCVBFRUQT-UHFFFAOYSA-N Y
Properties
Molecular formula	C25H48N6O8
Molar mass	560.68 g mol−1
log P	−0.614
Acidity (pKa)	9.079
Basicity (pKb)	4.918
Pharmacology
Routes of administration	Intramuscular Intraperitoneal Intravenous Oral Subcutaneous
Elimination half-life	6 hours
Related compounds
Related alkanamides	Stearamidopropyl dimethylamine
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

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. 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 medication needed in a basic health system.

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 (SQ infusion) 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 America, the drug is not FDA-approved for this use.

Deferoxamine is also used to minimize Doxorubicin Cardiotoxic side effects.

Deferoxamine has also been used in the treatment of a patient with aceruloplasminemia.

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. A recent study also shows that it speeds healing of nerve damage (and minimizes the extent of recent nerve trauma). Deferoxamine may modulate expression and release of inflammatory mediators by specific cell types.

Research

Deferoxamine is being studied as a treatment for spinal cord injury.

See also

• Chelation therapy

References

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

UpToDate Contents

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• 1. 鉄キレート薬：選択肢、投与量、副作用 iron chelators choice of agent dosing and adverse effects
• 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. ムコール症（接合真菌症） mucormycosis zygomycosis

English Journal

• Hemin uptake and release by neurons and glia.

• Chen-Roetling J, Cai Y, Lu X, Regan RF.Author information Department of Emergency Medicine, Thomas Jefferson University , Philadelphia, PA , USA.AbstractAbstract Hemin accumulates in intracerebral hematomas and may contribute to cell injury in adjacent tissue. Despite its relevance to hemorrhagic CNS insults, very little is known about hemin trafficking by neural cells. In the present study, hemin uptake and release were quantified in primary murine cortical cultures, and the effect of the hemin-binding compound deferoxamine (DFO) was assessed. Net uptake of (55)Fe-hemin was similar in mixed neuron-glia, neuron, and glia cultures, but was 2.6-3.6-fold greater in microglia cultures. After washout, 40-60% of the isotope signal was released by mixed neuron-glia cultures into albumin-containing medium within 24 h. Inhibiting hemin breakdown with tin protoporphyrin IX (SnPPIX) had minimal effect, while release of the fluorescent hemin analog zinc mesoporphyrin was quantitatively similar to that of (55)Fe-hemin. Isotope was released most rapidly by neurons (52.2 ± 7.2% at 2 h), compared with glia (15.6 ± 1.3%) and microglia (17.6 ± 0.54%). DFO did not alter (55)Fe-hemin uptake, but significantly increased its release. Mixed cultures treated with 10 μM hemin for 24 h sustained widespread neuronal loss that was attenuated by DFO. Concomitant treatment with SnPPIX had no effect on either enhancement of isotope release by DFO or neuroprotection. These results suggest that in the presence of a physiologic albumin concentration, hemin uptake by neural cells is followed by considerable extracellular release. Enhancement of this release by DFO may contribute to its protective effect against hemin toxicity.
• Free radical research.Free Radic Res.2014 Feb;48(2):200-5. doi: 10.3109/10715762.2013.859386. Epub 2013 Nov 19.
• Abstract Hemin accumulates in intracerebral hematomas and may contribute to cell injury in adjacent tissue. Despite its relevance to hemorrhagic CNS insults, very little is known about hemin trafficking by neural cells. In the present study, hemin uptake and release were quantified in primary murine
• PMID 24164169

• Hypoxia inducible factor-1α mediates iron uptake which induces inflammatory response in amoeboid microglial cells in developing periventricular white matter through MAP kinase pathway.

• Rathnasamy G1, Ling EA1, Kaur C2.Author information 1Department of Anatomy, MD10, 4 Medical Drive, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.2Department of Anatomy, MD10, 4 Medical Drive, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore. Electronic address: antkaurc@nus.edu.sg.AbstractIron accumulation occurs in tissues such as periventricular white matter (PWM) in response to hypoxic injuries, and microglial cells sequester excess iron following hypoxic exposure. As hypoxia has a role in altering the expression of proteins involved in iron regulation, this study was aimed at examining the interaction between hypoxia inducible factor (HIF)-1α and proteins involved in iron transport in microglial cells, and evaluating the mechanistic action of deferoxamine and KC7F2 (an inhibitor of HIF-1α) in iron mediated hypoxic injury. Treating the microglial cultures with KC7F2, led to decreased expression of transferrin receptor and divalent metal transporter-1. Administration of deferoxamine or KC7F2 to hypoxic microglial cells enhanced extracellular signal-regulated kinase (ERK) phosphorylation (p-ERK), but decreased the phosphorylation of p38 (p-p38). The increased p-ERK further phosphorylated the cAMP response element-binding protein (p-CREB) which in turn may have resulted in the increased mitogen activated protein kinase (MAPK) phosphatase 1 (MKP1), known to dephosphorylate MAPKs. Consistent with the decrease in p-p38, the production of pro-inflammatory cytokines TNF-α and IL-1β was reduced in hypoxic microglia treated with deferoxamine and SB 202190, an inhibitor for p38. This suggests that the anti-inflammatory effect exhibited by deferoxamine is by inhibition of p-p38 induced inflammation through the pERK-pCREB-MKP1 pathway, whereas that of KC7F2 requires further investigation. The present results suggest that HIF-1α may mediate iron accumulation in hypoxic microglia and KC7F2, similar to deferoxamine, might provide limited protection against iron induced PWMD.
• Neuropharmacology.Neuropharmacology.2014 Feb;77:428-40. doi: 10.1016/j.neuropharm.2013.10.024. Epub 2013 Nov 1.
• Iron accumulation occurs in tissues such as periventricular white matter (PWM) in response to hypoxic injuries, and microglial cells sequester excess iron following hypoxic exposure. As hypoxia has a role in altering the expression of proteins involved in iron regulation, this study was aimed at exa
• PMID 24184387

• FTIR study of protective action of deferoxamine and deferiprone on the kidney tissues of aluminum loaded mice.

• Sivakumar S, Khatiwada CP, Sivasubramanian J, Raja B.Author information Department of Physics, Annamalai University, Annamalai Nagar, Tamilnadu 608002, India. Electronic address: girihari777@yahoo.com.AbstractThe present study was designed to evaluate the FTIR spectra of the aluminum exposed kidney tissues and recovered by chelating agents DFO and DFP then showed significant alteration on the major biochemical constituents such as lipids, proteins and glycogen at molecular level. The significant increased in the peak area of glycogen from 0.006±0.001 to 0.187±0.032 may be the interruption of aluminum in the calcium metabolism and the reduced level of calcium. The peak area value of amide A significantly decreased from control (4.931±1.446) to aluminum (1.234±0.052), but improved by DFP and DFO+DFP from 2.658±0.153 to 3.252±0.070 respectively. Amide I and amide II peak area values also decreased from 1.690±0.133 to 0.811±0.192 and 1.158±0.050 to 0.489±0.047 but treated with DFP and DFO+DFP significantly improved. This result suggests an alteration in the protein profile. The absence of Olefinic=CH stretching band, C=O stretching of triglycerides and ring breathing mode in the DNA bases in aluminum exposure kidney suggests an altered lipid levels. Treated with DFP and DFO+DFP mice were considerably increased in lipid peroxidative markers. Further, assessed the activities of enzymatic antioxidants and measured the levels of nonenzymatic antioxidants. Concentrations of trace elements were found by ICP-OES. Histopathology of chelating agents treated kidney showed reduced renal damage in aluminum induced mice. Thus, histopathological findings confirmed the biochemical observations of this study. This results demonstrated that FTIR spectroscopy can be successfully applied to toxicological and biotoxicology studies.
• Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2014 Jan 24;118:488-97. doi: 10.1016/j.saa.2013.09.011. Epub 2013 Sep 13.
• The present study was designed to evaluate the FTIR spectra of the aluminum exposed kidney tissues and recovered by chelating agents DFO and DFP then showed significant alteration on the major biochemical constituents such as lipids, proteins and glycogen at molecular level. The significant increase
• PMID 24080580

Japanese Journal

• 鉄を視点とするアスベスト発がんの解明と予防・診断・治療への応用の可能性

• 豊國 伸哉
• 肺癌 49(4), 362-367, 2009
• 目的．アスベストの発がん機構を解明する．方法．アスベスト（UICC: クリソタイル，クロシドライト，アモサイト）の物理化学的な性質を再検討する一方，培養細胞や実験動物個体にアスベストの投与を行い，生物学的性質を詳細に評価した．結果．ラジカル発生の触媒能はアモサイト＞クロシドライト＞＞＞クリソタイルであり，それは種々のキレート剤の存在で修飾を受けた．貪食細胞以外に，中皮細胞や腺癌細胞もアスベスト繊維 …
• NAID 130000122998

• A Comparison between the Acid-Catalysed Reactions of Some Dihydroxamic Acids, Monohydroxamic Acids and Desferal

• Ghosh Kallol K.,Patle Shyam K.,Sharma Pokhraj [他],RAJPUT Surendra Kumar
• Bulletin of the Chemical Society of Japan 76(2), 283-290, 2003-02-15
• NAID 10010538404

• A Comparison between the Acid-Catalysed Reactions of Some Dihydroxamic Acids, Monohydroxamic Acids and Desferal.

• Ghosh Kallol K.,Patle Shyam Kumar,Sharma Pokhraj,Rajput Surendra Kumar
• Bulletin of the Chemical Society of Japan 76(2), 283-290, 2003
• … A comparison of the kinetic data with those from the hydrolysis of simple monohydroxamic acid, (acetohydroxamic acid [AHA] CH3CONHOH, benzohydroxamic acid [BHA] C6H5CONHOH) and the natural trihydroxamate-based siderophore desferal (DFB) revealed that the hydrolytic stability sequence of the compounds is generally: BHA > …
• NAID 130004058494

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