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Record Information
Version4.0
Creation Date2013-05-17 01:20:31 UTC
Update Date2017-09-27 08:43:47 UTC
HMDB IDHMDB0060433
Secondary Accession Numbers
  • HMDB60433
Metabolite Identification
Common NameAldophosphamide
DescriptionDetoxification of cyclophosphamide is effected, in part, by hepatic class 1 aldehyde dehydrogenase (ALDH-1)-catalyzed oxidation of aldophosphamide, a pivotal aldehyde intermediate, to the nontoxic metabolite, carboxyphosphamide. Detoxification of aldophosphamide may also be effected by enzymes, viz. Thus, NAD-linked oxidation and NADPH-linked reduction of aldophosphamide catalyzed by relevant erythrocyte enzymes were quantified. (PMID: 9394035 ) Class 1 aldehyde dehydrogenases (ALDH-1) function as drug resistance gene products by catalyzing the irreversible conversion of aldophosphamide, an active metabolite of cyclophosphamide, to an inert compound. (PMID: 9322086 )
Structure
Thumb
Synonyms
ValueSource
Cyclophosphamide-mustardMeSH
Cyp-mustardMeSH
Chemical FormulaC7H15Cl2N2O3P
Average Molecular Weight277.085
Monoisotopic Molecular Weight276.019734282
IUPAC Name3-({amino[bis(2-chloroethyl)amino]phosphoryl}oxy)propanal
Traditional Namealdophosphamide
CAS Registry NumberNot Available
SMILES
NP(=O)(OCCC=O)N(CCCl)CCCl
InChI Identifier
InChI=1S/C7H15Cl2N2O3P/c8-2-4-11(5-3-9)15(10,13)14-7-1-6-12/h6H,1-5,7H2,(H2,10,13)
InChI KeyQMGUSPDJTPDFSF-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as nitrogen mustard compounds. These are compounds having two beta-haloalkyl groups bound to a nitrogen atom.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic nitrogen compounds
Sub ClassOrganonitrogen compounds
Direct ParentNitrogen mustard compounds
Alternative Parents
Substituents
  • Nitrogen mustard
  • Phosphoric monoester diamide
  • Organic phosphoric acid derivative
  • Phosphoric acid ester
  • Organic phosphoric acid amide
  • Alpha-hydrogen aldehyde
  • Organic oxide
  • Organooxygen compound
  • Organochloride
  • Organopnictogen compound
  • Organohalogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Aldehyde
  • Alkyl halide
  • Alkyl chloride
  • Hydrocarbon derivative
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Organ and components:

Source:

Role

Biological role:

Physical Properties
StateNot Available
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility13.6 g/LALOGPS
logP0.55ALOGPS
logP-0.46ChemAxon
logS-1.3ALOGPS
pKa (Strongest Acidic)13.08ChemAxon
pKa (Strongest Basic)-0.069ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.63 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity60.54 m³·mol⁻¹ChemAxon
Polarizability24.82 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Kidney
  • Liver
Pathways
NameSMPDB/PathwhizKEGG
Cyclophosphamide Metabolism PathwayPw000580Pw000580 greyscalePw000580 simpleNot Available
Cyclophosphamide PathwayPw000248Pw000248 greyscalePw000248 simpleNot Available
Displaying all 2 entries
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableNormal
    details
    UrineExpected but not Quantified Not AvailableNot AvailableNormal
      details
      Abnormal Concentrations
      Not Available
      Associated Disorders and Diseases
      Disease ReferencesNone
      Associated OMIM IDsNone
      DrugBank IDNot Available
      DrugBank Metabolite IDDBMET00658
      Phenol Explorer Compound IDNot Available
      Phenol Explorer Metabolite IDNot Available
      FoodDB IDNot Available
      KNApSAcK IDNot Available
      Chemspider IDNot Available
      KEGG Compound IDC07645
      BioCyc IDNot Available
      BiGG IDNot Available
      Wikipedia LinkCyclophosphamide
      METLIN IDNot Available
      PubChem Compound0
      PDB IDNot Available
      ChEBI IDNot Available
      References
      Synthesis ReferenceNot Available
      Material Safety Data Sheet (MSDS)Not Available
      General References
      1. Magrane M: UniProt Knowledgebase: a hub of integrated protein data. Database (Oxford). 2011 Mar 29;2011:bar009. doi: 10.1093/database/bar009. Print 2011. [PubMed:21447597 ]
      2. Dockham PA, Sreerama L, Sladek NE: Relative contribution of human erythrocyte aldehyde dehydrogenase to the systemic detoxification of the oxazaphosphorines. Drug Metab Dispos. 1997 Dec;25(12):1436-41. [PubMed:9394035 ]
      3. Bunting KD, Townsend AJ: De novo expression of transfected human class 1 aldehyde dehydrogenase (ALDH) causes resistance to oxazaphosphorine anti-cancer alkylating agents in hamster V79 cell lines. Elevated class 1 ALDH activity is closely correlated with reduction in DNA interstrand cross-linking and lethality. J Biol Chem. 1996 May 17;271(20):11884-90. [PubMed:8662658 ]
      4. Bunting KD, Webb M, Giorgianni F, Galipeau J, Blakley RL, Townsend AJ, Sorrentino BP: Coding region-specific destabilization of mRNA transcripts attenuates expression from retroviral vectors containing class 1 aldehyde dehydrogenase cDNAs. Hum Gene Ther. 1997 Sep 1;8(13):1531-43. [PubMed:9322086 ]

      Enzymes

      General function:
      Involved in oxidoreductase activity
      Specific function:
      ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. This protein preferentially oxidizes aromatic aldehyde substrates. It may play a role in the oxidation of toxic aldehydes.
      Gene Name:
      ALDH3A1
      Uniprot ID:
      P30838
      Molecular weight:
      50394.57
      Reactions
      Aldophosphamide + NAD + Water → Carboxyphosphamide + NADH + Hydrogen Iondetails
      Aldophosphamide + NADP + Water → Carboxyphosphamide + NADPH + Hydrogen Iondetails
      General function:
      Involved in oxidoreductase activity
      Specific function:
      Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Seems to be the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development and also in the development of the olfactory system (By similarity).
      Gene Name:
      ALDH1A3
      Uniprot ID:
      P47895
      Molecular weight:
      56107.995
      Reactions
      Aldophosphamide + NAD + Water → Carboxyphosphamide + NADH + Hydrogen Iondetails
      Aldophosphamide + NADP + Water → Carboxyphosphamide + NADPH + Hydrogen Iondetails
      General function:
      Involved in zinc ion binding
      Specific function:
      Not Available
      Gene Name:
      ADH4
      Uniprot ID:
      P08319
      Molecular weight:
      40221.335
      Reactions
      Aldophosphamide + NADH + Hydrogen Ion → Alcophosphamide + NADdetails
      General function:
      Involved in oxidoreductase activity
      Specific function:
      Not Available
      Gene Name:
      ALDH3B2
      Uniprot ID:
      P48448
      Molecular weight:
      42623.62
      Reactions
      Aldophosphamide + NAD + Water → Carboxyphosphamide + NADH + Hydrogen Iondetails
      Aldophosphamide + NADP + Water → Carboxyphosphamide + NADPH + Hydrogen Iondetails
      General function:
      Involved in oxidoreductase activity
      Specific function:
      Oxidizes medium and long chain saturated and unsaturated aldehydes. Metabolizes also benzaldehyde. Low activity towards acetaldehyde and 3,4-dihydroxyphenylacetaldehyde. May not metabolize short chain aldehydes. May use both NADP(+) and NAD(+) as cofactors. May have a protective role against the cytotoxicity induced by lipid peroxidation.
      Gene Name:
      ALDH3B1
      Uniprot ID:
      P43353
      Molecular weight:
      51839.245
      Reactions
      Aldophosphamide + NAD + Water → Carboxyphosphamide + NADH + Hydrogen Iondetails
      Aldophosphamide + NADP + Water → Carboxyphosphamide + NADPH + Hydrogen Iondetails
      General function:
      Involved in zinc ion binding
      Specific function:
      Class-III ADH is remarkably ineffective in oxidizing ethanol, but it readily catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione.
      Gene Name:
      ADH5
      Uniprot ID:
      P11766
      Molecular weight:
      39723.945
      Reactions
      Aldophosphamide + NADH + Hydrogen Ion → Alcophosphamide + NADdetails
      General function:
      Involved in zinc ion binding
      Specific function:
      Not Available
      Gene Name:
      ADH1B
      Uniprot ID:
      P00325
      Molecular weight:
      39835.17
      Reactions
      Aldophosphamide + NADH + Hydrogen Ion → Alcophosphamide + NADdetails
      General function:
      Involved in zinc ion binding
      Specific function:
      Could function in retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation. Medium-chain (octanol) and aromatic (m-nitrobenzaldehyde) compounds are the best substrates. Ethanol is not a good substrate but at the high ethanol concentrations reached in the digestive tract, it plays a role in the ethanol oxidation and contributes to the first pass ethanol metabolism.
      Gene Name:
      ADH7
      Uniprot ID:
      P40394
      Molecular weight:
      41480.985
      Reactions
      Aldophosphamide + NADH + Hydrogen Ion → Alcophosphamide + NADdetails
      General function:
      Involved in zinc ion binding
      Specific function:
      Not Available
      Gene Name:
      ADH1A
      Uniprot ID:
      P07327
      Molecular weight:
      39858.37
      Reactions
      Aldophosphamide + NADH + Hydrogen Ion → Alcophosphamide + NADdetails
      General function:
      Involved in zinc ion binding
      Specific function:
      Not Available
      Gene Name:
      ADH6
      Uniprot ID:
      P28332
      Molecular weight:
      39072.275
      Reactions
      Aldophosphamide + NADH + Hydrogen Ion → Alcophosphamide + NADdetails
      General function:
      Involved in zinc ion binding
      Specific function:
      Not Available
      Gene Name:
      ADH1C
      Uniprot ID:
      P00326
      Molecular weight:
      39867.27
      Reactions
      Aldophosphamide + NADH + Hydrogen Ion → Alcophosphamide + NADdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
      Gene Name:
      GSTM2
      Uniprot ID:
      P28161
      Molecular weight:
      25744.395
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
      Gene Name:
      GSTM1
      Uniprot ID:
      P09488
      Molecular weight:
      25711.555
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in protein disulfide oxidoreductase activity
      Specific function:
      Significant glutathione conjugating activity is found only with the model substrate, 1-chloro-2,4-dinitrobenzene (CDNB).
      Gene Name:
      GSTK1
      Uniprot ID:
      Q9Y2Q3
      Molecular weight:
      31565.605
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Also functions as a glutathione peroxidase.
      Gene Name:
      MGST3
      Uniprot ID:
      O14880
      Molecular weight:
      16516.185
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May govern uptake and detoxification of both endogenous compounds and xenobiotics at the testis and brain blood barriers.
      Gene Name:
      GSTM3
      Uniprot ID:
      P21266
      Molecular weight:
      26559.32
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
      Gene Name:
      GSTA1
      Uniprot ID:
      P08263
      Molecular weight:
      25630.785
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Has a wide substrate specificity.
      Gene Name:
      MGST1
      Uniprot ID:
      P10620
      Molecular weight:
      17598.45
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Active on 1-chloro-2,4-dinitrobenzene.
      Gene Name:
      GSTM4
      Uniprot ID:
      Q03013
      Molecular weight:
      25561.095
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
      Gene Name:
      GSTM5
      Uniprot ID:
      P46439
      Molecular weight:
      25674.455
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in enzyme activator activity
      Specific function:
      Can catalyze the production of LTC4 from LTA4 and reduced glutathione. Can catalyze the conjugation of 1-chloro-2,4-dinitrobenzene with reduced glutathione.
      Gene Name:
      MGST2
      Uniprot ID:
      Q99735
      Molecular weight:
      16620.4
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Has also glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid.
      Gene Name:
      GSTO1
      Uniprot ID:
      P78417
      Molecular weight:
      27565.6
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Not Available
      Gene Name:
      GSTA5
      Uniprot ID:
      Q7RTV2
      Molecular weight:
      25721.725
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
      Gene Name:
      GSTA2
      Uniprot ID:
      P09210
      Molecular weight:
      25663.675
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively.
      Gene Name:
      GSTA3
      Uniprot ID:
      Q16772
      Molecular weight:
      25301.355
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE).
      Gene Name:
      GSTA4
      Uniprot ID:
      O15217
      Molecular weight:
      25703.905
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Exhibits glutathione-dependent thiol transferase activity. Has high dehydroascorbate reductase activity and may contribute to the recycling of ascorbic acid. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA).
      Gene Name:
      GSTO2
      Uniprot ID:
      Q9H4Y5
      Molecular weight:
      24399.09
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Posttranslational modification, protein turnover, chaperones
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-nitrobenzyl chloride and 4-nitrophenethyl bromide. Displays glutathione peroxidase activity with cumene hydroperoxide.
      Gene Name:
      GSTT1
      Uniprot ID:
      P30711
      Molecular weight:
      27334.755
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Involved in glutathione transferase activity
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
      Gene Name:
      GSTP1
      Uniprot ID:
      P09211
      Molecular weight:
      23355.625
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails
      General function:
      Not Available
      Specific function:
      Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Has a sulfatase activity.
      Gene Name:
      GSTT2B
      Uniprot ID:
      P0CG30
      Molecular weight:
      27506.715
      Reactions
      Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Waterdetails