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Record Information
Version3.6
Creation Date2013-05-17 01:20:31 UTC
Update Date2016-02-11 08:05:45 UTC
HMDB IDHMDB60433
Secondary Accession NumbersNone
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
SynonymsNot Available
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=1/C7H15Cl2N2O3P/c8-2-4-11(5-3-9)15(10,13)14-7-1-6-12/h6H,1-5,7H2,(H2,10,13)
InChI KeyInChIKey=QMGUSPDJTPDFSF-UHFFFAOYNA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as nitrogen mustard compounds. These are compounds having two beta-haloalkyl groups bound to a nitrogen atom.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassNitrogen mustard compounds
Sub ClassNot Available
Direct ParentNitrogen mustard compounds
Alternative Parents
Substituents
  • Nitrogen mustard
  • Phosphoric monoester diamide
  • Phosphoric acid ester
  • Organic phosphoric acid derivative
  • Alpha-hydrogen aldehyde
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl chloride
  • Aldehyde
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug metabolite
Biofunction
  • Waste products
ApplicationNot Available
Cellular locations
  • Cytoplasm
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 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity60.54 m3·mol-1ChemAxon
Polarizability24.82 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
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
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableNormal
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableNormal
  • Not Applicable
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 LinkNot Available
NuGOwiki LinkHMDB60433
Metagene LinkHMDB60433
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Magrane M, Consortium U: UniProt Knowledgebase: a hub of integrated protein data. Database (Oxford). 2011 Mar 29;2011:bar009. doi: 10.1093/database/bar009. Print 2011. [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. [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. [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. [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