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Amifostine

July 24, 2017
Common Name

Amifostine Description

Amifostine is only found in individuals that have used or taken this drug. It is a phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [PubChem]The thiol metabolite is responsible for most of the cytoprotective and radioprotective properties of amifostine. It is readily taken up by cells where it binds to and detoxifies reactive metabolites of platinum and alkylating agents as well as scavenges free radicals. Other possible effects include inhibition of apoptosis, alteration of gene expression and modification of enzyme activity. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source AmifostinaChEBI AmifostinumChEBI EthyolChEBI Amifostine ethiofosHMDB Aminopropylaminoethyl thiophosphateHMDB ApaetpHMDB EthiofosHMDB GammaphosHMDB SAPEPHMDB WR-1065HMDB Alza brand OF amifostineMeSH Amifostine disodium saltMeSH Amifostine trihydrateMeSH Anhydrous, amifostineMeSH Anhydrous, ethiofosMeSH Monohydrochloride, amifostineMeSH S-(N-(3-Aminopropyl)-2-aminoethyl)thiophosphoric acidMeSH Schering plough brand OF amifostineMeSH Amifostine alza brandMeSH Amifostine monohydrochlorideMeSH Disodium salt, amifostineMeSH Trihydrate, amifostineMeSH US bioscience brand OF amifostineMeSH Amifostine lilly brandMeSH Aminopropylaminoethylthiophosphoric acidMeSH Essex brand OF amifostineMeSH Ethiofos anhydrousMeSH Lilly brand OF amifostineMeSH Schering-plough brand OF amifostineMeSH Amifostine anhydrousMeSH Amifostine essex brandMeSH Amifostine monohydrateMeSH Amifostine schering-plough brandMeSH Aminopropyl aminoethylthiophosphateMeSH AminopropylaminoethylthiophosphateMeSH Monohydrate, amifostineMeSH

Chemical Formlia

C5H15N2O3PS Average Molecliar Weight

214.223 Monoisotopic Molecliar Weight

214.054099558 IUPAC Name

({2-[(3-aminopropyl)amino]ethyl}slifanyl)phosphonic acid Traditional Name

amifostine CAS Registry Number

20537-88-6 SMILES

NCCCNCCSP(O)(O)=O

InChI Identifier

InChI=1S/C5H15N2O3PS/c6-2-1-3-7-4-5-12-11(8,9)10/h7H,1-6H2,(H2,8,9,10)

InChI Key

JKOQGQFVAUAYPM-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as organothiophosphorus compounds. These are organic derivatives of thiophosphonic acid, thiophosphoric acid, dithiophosphoric acid, or phosphorotrithioic acid, or derivatives thereof. Thiophosphonic acid, dithiophosphoric acid, thiophosphoric acid, and phosphorotrithioic acid are thiophosphorus compounds with the formlia OP(O)(=S), OP(S)(=S)O, OP(O)(=S)O, and OP(=S)(S)S, respectively. Kingdom

Chemical entities Super Class

Organic compounds Class

Organophosphorus compounds Sub Class

Organothiophosphorus compounds Direct Parent

Organothiophosphorus compounds Alternative Parents

  • Slifenyl compounds
  • Dialkylamines
  • Organopnictogen compounds
  • Organic oxides
  • Monoalkylamines
  • Hydrocarbon derivatives

    • Substituents

  • Slifenyl compound
  • Secondary amine
  • Organothiophosphorus compound
  • Secondary aliphatic amine
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Primary amine
  • Organoslifur compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Amine
  • Aliphatic acyclic compound

    • Molecliar Framework

    Aliphatic acyclic compounds External Descriptors

  • organic thiophosphate (CHEBI:2636 )
  • diamine (CHEBI:2636 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Radiation-Protective Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility1.87e+01 g/LNot Available LogP-1.9Not Available

    Predicted Properties

    Property Value Source Water Solubility18.7 mg/mLALOGPS logP-1.4ALOGPS logP-3.7ChemAxon logS-1.1ALOGPS pKa (Strongest Acidic)2.06ChemAxon pKa (Strongest Basic)11.01ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count5ChemAxon Hydrogen Donor Count4ChemAxon Polar Surface Area95.58 Å2ChemAxon Rotatable Bond Count7ChemAxon Refractivity51.28 m3·mol-1ChemAxon Polarizability21.01 Å3ChemAxon Number of Rings0ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-0002-0900000000-5350b8c906608c1eb7e4View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-0002-0900000000-bcddc871edb434e577aeView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-0002-2900000000-58ff84f991edcac36e7dView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-05nb-9200000000-ef847b9b156a08e7fa17View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-0a4l-9000000000-c58215f6bca055f13ab7View in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01143

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01143

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01143 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    2056 KEGG Compound ID

    C06819 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Amifostine NuGOwiki Link

    HMDB15274 Metagene Link

    HMDB15274 METLIN ID

    Not Available PubChem Compound

    2141 PDB ID

    Not Available ChEBI ID

    2636

    Product: MTT

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Santini V, Giles FJ: The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999 Nov;84(11):1035-42. [PubMed:10553165 ]
    2. Xu Y, Parmar K, Du F, Price BD, Sun Y: The radioprotective agent WR1065 protects cells from radiation damage by regulating the activity of the Tip60 acetyltransferase. Int J Biochem Mol Biol. 2011;2(4):295-302. Epub 2011 Oct 20. [PubMed:22187663 ]
    3. Murley JS, Kataoka Y, Miller RC, Li JJ, Woloschak G, Grdina DJ: SOD2-mediated effects induced by WR1065 and low-dose ionizing radiation on micronucleus formation in RKO human colon carcinoma cells. Radiat Res. 2011 Jan;175(1):57-65. doi: 10.1667/RR2349.1. Epub 2010 Nov 8. [PubMed:21175348 ]
    4. Poirier MC, Olivero OA, Hardy AW, Franchini G, Borojerdi JP, Walker VE, Walker DM, Shearer GM: Antiretroviral activity of the aminothiol WR1065 against Human Immunodeficiency virus (HIV-1) in vitro and Simian Immunodeficiency virus (SIV) ex vivo. AIDS Res Ther. 2009 Nov 6;6:24. doi: 10.1186/1742-6405-6-24. [PubMed:19895691 ]
    5. Grdina DJ, Murley JS, Miller RC, Mauceri HJ, Sutton HG, Thirman MJ, Li JJ, Woloschak GE, Weichselbaum RR: A manganese superoxide dismutase (SOD2)-mediated adaptive response. Radiat Res. 2013 Feb;179(2):115-24. doi: 10.1667/RR3126.2. Epub 2012 Dec 13. [PubMed:23237540 ]
    6. Murley JS, Baker KL, Miller RC, Darga TE, Weichselbaum RR, Grdina DJ: SOD2-mediated adaptive responses induced by low-dose ionizing radiation via TNF signaling and amifostine. Free Radic Biol Med. 2011 Nov 15;51(10):1918-25. doi: 10.1016/j.freeradbiomed.2011.08.032. Epub 2011 Sep 3. [PubMed:21945096 ]
    7. Walker DM, Kajon AE, Torres SM, Carter MM, McCash CL, Swenberg JA, Upton PB, Hardy AW, Olivero OA, Shearer GM, Poirier MC, Walker VE: WR1065 mitigates AZT-ddI-induced mutagenesis and inhibits viral replication. Environ Mol Mutagen. 2009 Jul;50(6):460-72. doi: 10.1002/em.20482. [PubMed:19334055 ]
    8. Mereniuk TR, Maranchuk RA, Schindler A, Penner-Chea J, Freschauf GK, Hegazy S, Lai R, Foley E, Weinfeld M: Genetic screening for synthetic lethal partners of polynucleotide kinase/phosphatase: potential for targeting SHP-1-depleted cancers. Cancer Res. 2012 Nov 15;72(22):5934-44. doi: 10.1158/0008-5472.CAN-12-0939. Epub 2012 Sep 7. [PubMed:22962271 ]

    Enzymes

    General function:
    Involved in catalytic activity
    Specific function:
    This isozyme may play a role in skeletal mineralization.
    Gene Name:
    ALPL
    Uniprot ID:
    P05186
    Molecular weight:
    57304.435
    References
    1. Shaw LM, Bonner H, Lieberman R: Pharmacokinetic profile of amifostine. Semin Oncol. 1996 Aug;23(4 Suppl 8):18-22. [PubMed:8783662 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Not Available
    Gene Name:
    ALPPL2
    Uniprot ID:
    P10696
    Molecular weight:
    57376.515
    References
    1. Capizzi RL: The preclinical basis for broad-spectrum selective cytoprotection of normal tissues from cytotoxic therapies by amifostine. Semin Oncol. 1999 Apr;26(2 Suppl 7):3-21. [PubMed:10348255 ]
    2. Orditura M, De Vita F, Roscigno A, Infusino S, Auriemma A, Iodice P, Ciaramella F, Abbate G, Catalano G: Amifostine: A selective cytoprotective agent of normal tissues from chemo-radiotherapy induced toxicity (Review). Oncol Rep. 1999 Nov-Dec;6(6):1357-62. [PubMed:10523712 ]
    3. Santini V, Giles FJ: The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999 Nov;84(11):1035-42. [PubMed:10553165 ]
    4. Plasswilm L, Hanjalic A, Hoeper J, Cordes N, Tannapfel A: Microvessel density and endothelial cell proliferation after amifostine (Ethyol) administration in vivo. Anticancer Res. 1999 Sep-Oct;19(5B):4241-5. [PubMed:10628381 ]
    5. Buschini A, Anceschi E, Carlo-Stella C, Regazzi E, Rizzoli V, Poli P, Rossi C: Amifostine (WR-2721) selective protection against melphalan genotoxicity. Leukemia. 2000 Sep;14(9):1642-51. [PubMed:10995012 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Involved primarily in ATP hydrolysis at the plasma membrane. Plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. In vitro, has a broad specificity, hydrolyzing other nucleoside 5 triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3,5-cAMP to AMP. May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling. Appears to modulate insulin sensitivity.
    Gene Name:
    ENPP1
    Uniprot ID:
    P22413
    Molecular weight:
    104923.58
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]

    PMID: 8071941

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