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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (9)transporters (1) Show 10 proteins XML

enzymes (9)transporters (1) Show 10 proteins

Record Information

Version

5.0

Status

Expected but not Quantified

Creation Date

2012-09-06 15:00:14 UTC

Update Date

2021-09-14 15:20:33 UTC

HMDB ID

HMDB0013856

Secondary Accession Numbers

HMDB13856

Metabolite Identification

Common Name

4-Hydroxycyclophosphamide

Description

4-Hydroxycyclophosphamide is a primary activation metabolite of cyclophosphamide and of mafosfamide (an experimental drug) after they partially metabolized by cytochrome P450 (PMID: 12021633 ). Cyclophosphamide is a chemotherapeutic used to suppress the immune system and to treat several cancers including lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer and small cell lung cancer. After cyclphosphamide is converted to 4-hydroxycyclophosphamide it is then partially tautomerized into aldophosphamide, which easily enters live cells whereupon it is partially detoxified into inactive carboxycyclophosphamide by the enzyme ALDH. 4-Hydroxycyclophosphamide is also an intermediate metabolite in the formation of phosphoramide mustard, the active metabolite, and acrolein, the metabolite responsible for much of the toxicity associated with cyclophosphamides (PMID: 7059981 ). 4-Hydroxycyclophosphamide is not cytotoxic at physiologic pH, readily diffuses into cells and spontaneously decomposes into the active phosphoramide mustard. In human liver microsomes, 4-Hydroxycyclophosphamide formation correlates with known phenotypic markers of CYP2B6 activity, specifically formation of (S)-2-ethyl-1,5-dimethyl-3,3-diphenyl pyrrolidine and hydroxybupropion. In addition, it is reported that the CYP2B6 genotype is not consistently related to 4-Hydroxycyclophosphamide formation in vitro or in vivo (PMID: 21976622 ). 4-Hydroxycyclophosphamide is only found in individuals who have consumed the drug cyclophosphamide.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

HMDB0013856
     RDKit          3D
4-Hydroxycyclophosphamide
 30 30  0  0  0  0  0  0  0  0999 V2000
   -0.3432   -1.8673    1.6329 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4817   -0.6995    0.6586 P   0  0  0  0  0  5  0  0  0  0  0  0
    1.0873   -0.1704    0.2072 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7649   -1.2125   -0.4488 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2243   -1.3861   -0.2592 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6495   -1.6094    1.4520 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    1.2895    1.1656   -0.1033 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5733    1.8208    0.3141 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5927    3.5286   -0.2812 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -1.4996    0.4886    1.3843 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8591    0.1577    0.9624 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0422   -1.2138    1.1482 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9898    0.4461   -0.4957 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9729   -0.2808   -1.3422 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3411   -1.3138   -0.6891 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4835   -1.1630   -1.5419 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2708   -2.1911   -0.1317 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.9021   -0.7217   -0.7683 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4613   -2.4331   -0.7115 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2346    1.2846   -1.2310 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.4713    1.8517    0.2535 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4840    1.2919    0.1015 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.5785    1.9618    1.4607 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3517    1.4576    1.0822 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5946    0.7647    1.5197 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9888   -1.4615    1.3126 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0258    0.2407   -0.8580 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8457    1.5353   -0.6371 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4997   -0.7070   -2.2199 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2318    0.4354   -1.7713 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  1  0
  4  5  1  0
  5  6  1  0
  3  7  1  0
  7  8  1  0
  8  9  1  0
  2 10  1  0
 10 11  1  0
 11 12  1  0
 11 13  1  0
 13 14  1  0
 14 15  1  0
 15  2  1  0
  4 16  1  0
  4 17  1  0
  5 18  1  0
  5 19  1  0
  7 20  1  0
  7 21  1  0
  8 22  1  0
  8 23  1  0
 10 24  1  0
 11 25  1  0
 12 26  1  0
 13 27  1  0
 13 28  1  0
 14 29  1  0
 14 30  1  0
M  END


  Mrv0541 06191310212D          

 15 15  0  0  0  0            999 V2000
    9.5786   -3.4674    0.0000 P   0  0  0  0  0  0  0  0  0  0  0  0
    9.9798   -2.7483    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.1815   -4.1864    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.7556   -3.4841    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.3099   -3.8600    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.5497   -2.0462    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7267   -2.0629    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3298   -2.7818    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3504   -4.1992    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.6075   -4.8970    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9464   -1.3146    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.1262   -4.9391    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    9.6366   -6.3309    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    9.2107   -5.6203    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9533   -4.9224    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0  0  0  0
  3  1  1  0  0  0  0
  4  1  1  0  0  0  0
  5  1  2  0  0  0  0
  6  2  1  0  0  0  0
  7  8  1  0  0  0  0
  8  4  1  0  0  0  0
  9  3  1  0  0  0  0
 10  3  1  0  0  0  0
 11  6  1  0  0  0  0
 12 15  1  0  0  0  0
 13 14  1  0  0  0  0
 14 10  1  0  0  0  0
 15  9  1  0  0  0  0
  7  6  1  0  0  0  0
M  END
> <DATABASE_ID>
HMDB0013856

> <DATABASE_NAME>
hmdb

> <SMILES>
OC1CCOP(=O)(N1)N(CCCl)CCCl

> <INCHI_IDENTIFIER>
InChI=1S/C7H15Cl2N2O3P/c8-2-4-11(5-3-9)15(13)10-7(12)1-6-14-15/h7,12H,1-6H2,(H,10,13)

> <INCHI_KEY>
RANONBLIHMVXAJ-UHFFFAOYSA-N

> <FORMULA>
C7H15Cl2N2O3P

> <MOLECULAR_WEIGHT>
277.085

> <EXACT_MASS>
276.019734282

> <JCHEM_ACCEPTOR_COUNT>
3

> <JCHEM_AVERAGE_POLARIZABILITY>
24.572307460036633

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
2

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
1

> <JCHEM_IUPAC>
2-[bis(2-chloroethyl)amino]-4-hydroxy-1,3,2λ⁵-oxazaphosphinan-2-one

> <ALOGPS_LOGP>
-0.02

> <JCHEM_LOGP>
-0.05733287299999987

> <ALOGPS_LOGS>
-1.09

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
1

> <JCHEM_PHYSIOLOGICAL_CHARGE>
0

> <JCHEM_PKA>
13.061607142859263

> <JCHEM_PKA_STRONGEST_ACIDIC>
10.67954718471601

> <JCHEM_PKA_STRONGEST_BASIC>
0.0051739710010082485

> <JCHEM_POLAR_SURFACE_AREA>
61.8

> <JCHEM_REFRACTIVITY>
59.09440000000001

> <JCHEM_ROTATABLE_BOND_COUNT>
5

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
2.25e+01 g/l

> <JCHEM_TRADITIONAL_IUPAC>
4-hydroxycyclophosphamide

> <JCHEM_VEBER_RULE>
0

$$$$

HMDB0013856
     RDKit          3D
4-Hydroxycyclophosphamide
 30 30  0  0  0  0  0  0  0  0999 V2000
   -0.3432   -1.8673    1.6329 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4817   -0.6995    0.6586 P   0  0  0  0  0  5  0  0  0  0  0  0
    1.0873   -0.1704    0.2072 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7649   -1.2125   -0.4488 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2243   -1.3861   -0.2592 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6495   -1.6094    1.4520 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    1.2895    1.1656   -0.1033 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5733    1.8208    0.3141 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5927    3.5286   -0.2812 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -1.4996    0.4886    1.3843 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8591    0.1577    0.9624 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0422   -1.2138    1.1482 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9898    0.4461   -0.4957 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9729   -0.2808   -1.3422 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3411   -1.3138   -0.6891 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4835   -1.1630   -1.5419 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2708   -2.1911   -0.1317 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.9021   -0.7217   -0.7683 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4613   -2.4331   -0.7115 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2346    1.2846   -1.2310 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.4713    1.8517    0.2535 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4840    1.2919    0.1015 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.5785    1.9618    1.4607 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3517    1.4576    1.0822 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5946    0.7647    1.5197 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9888   -1.4615    1.3126 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0258    0.2407   -0.8580 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8457    1.5353   -0.6371 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4997   -0.7070   -2.2199 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2318    0.4354   -1.7713 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  1  0
  4  5  1  0
  5  6  1  0
  3  7  1  0
  7  8  1  0
  8  9  1  0
  2 10  1  0
 10 11  1  0
 11 12  1  0
 11 13  1  0
 13 14  1  0
 14 15  1  0
 15  2  1  0
  4 16  1  0
  4 17  1  0
  5 18  1  0
  5 19  1  0
  7 20  1  0
  7 21  1  0
  8 22  1  0
  8 23  1  0
 10 24  1  0
 11 25  1  0
 12 26  1  0
 13 27  1  0
 13 28  1  0
 14 29  1  0
 14 30  1  0
M  END

HEADER    PROTEIN                                 19-JUN-13   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   19-JUN-13         0                                  
HETATM    1  P   UNK     0      17.880  -6.472   0.000  0.00  0.00           P+0
HETATM    2  N   UNK     0      18.629  -5.130   0.000  0.00  0.00           N+0
HETATM    3  N   UNK     0      17.139  -7.815   0.000  0.00  0.00           N+0
HETATM    4  O   UNK     0      16.344  -6.504   0.000  0.00  0.00           O+0
HETATM    5  O   UNK     0      19.245  -7.205   0.000  0.00  0.00           O+0
HETATM    6  C   UNK     0      17.826  -3.820   0.000  0.00  0.00           C+0
HETATM    7  C   UNK     0      16.290  -3.851   0.000  0.00  0.00           C+0
HETATM    8  C   UNK     0      15.549  -5.193   0.000  0.00  0.00           C+0
HETATM    9  C   UNK     0      15.587  -7.839   0.000  0.00  0.00           C+0
HETATM   10  C   UNK     0      17.934  -9.141   0.000  0.00  0.00           C+0
HETATM   11  O   UNK     0      18.567  -2.454   0.000  0.00  0.00           O+0
HETATM   12 Cl   UNK     0      13.302  -9.220   0.000  0.00  0.00          Cl+0
HETATM   13 Cl   UNK     0      17.988 -11.818   0.000  0.00  0.00          Cl+0
HETATM   14  C   UNK     0      17.193 -10.491   0.000  0.00  0.00           C+0
HETATM   15  C   UNK     0      14.846  -9.188   0.000  0.00  0.00           C+0
CONECT    1    2    3    4    5                                             
CONECT    2    1    6                                                       
CONECT    3    1    9   10                                                  
CONECT    4    1    8                                                       
CONECT    5    1                                                            
CONECT    6    2   11    7                                                  
CONECT    7    8    6                                                       
CONECT    8    7    4                                                       
CONECT    9    3   15                                                       
CONECT   10    3   14                                                       
CONECT   11    6                                                            
CONECT   12   15                                                            
CONECT   13   14                                                            
CONECT   14   13   10                                                       
CONECT   15   12    9                                                       
MASTER        0    0    0    0    0    0    0    0   15    0   30    0
END

COMPND    HMDB0013856
HETATM    1  O1  UNL     1      -0.343  -1.867   1.633  1.00  0.00           O  
HETATM    2  P1  UNL     1      -0.482  -0.699   0.659  1.00  0.00           P  
HETATM    3  N1  UNL     1       1.087  -0.170   0.207  1.00  0.00           N  
HETATM    4  C1  UNL     1       1.765  -1.212  -0.449  1.00  0.00           C  
HETATM    5  C2  UNL     1       3.224  -1.386  -0.259  1.00  0.00           C  
HETATM    6 CL1  UNL     1       3.649  -1.609   1.452  1.00  0.00          CL  
HETATM    7  C3  UNL     1       1.289   1.166  -0.103  1.00  0.00           C  
HETATM    8  C4  UNL     1       2.573   1.821   0.314  1.00  0.00           C  
HETATM    9 CL2  UNL     1       2.593   3.529  -0.281  1.00  0.00          CL  
HETATM   10  N2  UNL     1      -1.500   0.489   1.384  1.00  0.00           N  
HETATM   11  C5  UNL     1      -2.859   0.158   0.962  1.00  0.00           C  
HETATM   12  O2  UNL     1      -3.042  -1.214   1.148  1.00  0.00           O  
HETATM   13  C6  UNL     1      -2.990   0.446  -0.496  1.00  0.00           C  
HETATM   14  C7  UNL     1      -1.973  -0.281  -1.342  1.00  0.00           C  
HETATM   15  O3  UNL     1      -1.341  -1.314  -0.689  1.00  0.00           O  
HETATM   16  H1  UNL     1       1.483  -1.163  -1.542  1.00  0.00           H  
HETATM   17  H2  UNL     1       1.271  -2.191  -0.132  1.00  0.00           H  
HETATM   18  H3  UNL     1       3.902  -0.722  -0.768  1.00  0.00           H  
HETATM   19  H4  UNL     1       3.461  -2.433  -0.711  1.00  0.00           H  
HETATM   20  H5  UNL     1       1.235   1.285  -1.231  1.00  0.00           H  
HETATM   21  H6  UNL     1       0.471   1.852   0.254  1.00  0.00           H  
HETATM   22  H7  UNL     1       3.484   1.292   0.102  1.00  0.00           H  
HETATM   23  H8  UNL     1       2.579   1.962   1.461  1.00  0.00           H  
HETATM   24  H9  UNL     1      -1.352   1.458   1.082  1.00  0.00           H  
HETATM   25  H10 UNL     1      -3.595   0.765   1.520  1.00  0.00           H  
HETATM   26  H11 UNL     1      -3.989  -1.462   1.313  1.00  0.00           H  
HETATM   27  H12 UNL     1      -4.026   0.241  -0.858  1.00  0.00           H  
HETATM   28  H13 UNL     1      -2.846   1.535  -0.637  1.00  0.00           H  
HETATM   29  H14 UNL     1      -2.500  -0.707  -2.220  1.00  0.00           H  
HETATM   30  H15 UNL     1      -1.232   0.435  -1.771  1.00  0.00           H  
CONECT    1    2    2
CONECT    2    3   10   15
CONECT    3    4    7
CONECT    4    5   16   17
CONECT    5    6   18   19
CONECT    7    8   20   21
CONECT    8    9   22   23
CONECT   10   11   24
CONECT   11   12   13   25
CONECT   12   26
CONECT   13   14   27   28
CONECT   14   15   29   30
END

HMDB0013856
     RDKit          3D
4-Hydroxycyclophosphamide
 30 30  0  0  0  0  0  0  0  0999 V2000
   -0.3432   -1.8673    1.6329 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4817   -0.6995    0.6586 P   0  0  0  0  0  5  0  0  0  0  0  0
    1.0873   -0.1704    0.2072 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7649   -1.2125   -0.4488 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2243   -1.3861   -0.2592 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6495   -1.6094    1.4520 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    1.2895    1.1656   -0.1033 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5733    1.8208    0.3141 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5927    3.5286   -0.2812 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -1.4996    0.4886    1.3843 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8591    0.1577    0.9624 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0422   -1.2138    1.1482 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9898    0.4461   -0.4957 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9729   -0.2808   -1.3422 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3411   -1.3138   -0.6891 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4835   -1.1630   -1.5419 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2708   -2.1911   -0.1317 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.9021   -0.7217   -0.7683 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4613   -2.4331   -0.7115 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2346    1.2846   -1.2310 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.4713    1.8517    0.2535 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4840    1.2919    0.1015 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.5785    1.9618    1.4607 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3517    1.4576    1.0822 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5946    0.7647    1.5197 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9888   -1.4615    1.3126 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0258    0.2407   -0.8580 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8457    1.5353   -0.6371 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4997   -0.7070   -2.2199 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2318    0.4354   -1.7713 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  1  0
  4  5  1  0
  5  6  1  0
  3  7  1  0
  7  8  1  0
  8  9  1  0
  2 10  1  0
 10 11  1  0
 11 12  1  0
 11 13  1  0
 13 14  1  0
 14 15  1  0
 15  2  1  0
  4 16  1  0
  4 17  1  0
  5 18  1  0
  5 19  1  0
  7 20  1  0
  7 21  1  0
  8 22  1  0
  8 23  1  0
 10 24  1  0
 11 25  1  0
 12 26  1  0
 13 27  1  0
 13 28  1  0
 14 29  1  0
 14 30  1  0
M  END

View in JSmol View Stereo Labels

Synonyms

Value	Source
Tetrahydro-2-(bis(2-chloroethyl)amino)-2H-1,3,2-oxazaphosphorin-4-ol 2-oxide	ChEBI
4-Hydroxycyclophosphamide, (cis)-isomer	HMDB
4-Hydroxycyclophosphamide, (trans)-isomer	HMDB

Chemical Formula

C₇H₁₅Cl₂N₂O₃P

Average Molecular Weight

277.085

Monoisotopic Molecular Weight

276.019734282

IUPAC Name

2-[bis(2-chloroethyl)amino]-4-hydroxy-1,3,2λ⁵-oxazaphosphinan-2-one

Traditional Name

4-hydroxycyclophosphamide

CAS Registry Number

40277-05-2

SMILES

OC1CCOP(=O)(N1)N(CCCl)CCCl

InChI Identifier

InChI=1S/C7H15Cl2N2O3P/c8-2-4-11(5-3-9)15(13)10-7(12)1-6-14-15/h7,12H,1-6H2,(H,10,13)

InChI Key

RANONBLIHMVXAJ-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as nitrogen mustard compounds. Nitrogen mustard compounds are compounds having two beta-haloalkyl groups bound to a nitrogen atom.

Kingdom

Organic compounds

Super Class

Organic nitrogen compounds

Class

Organonitrogen compounds

Sub Class

Nitrogen mustard compounds

Direct Parent

Nitrogen mustard compounds

Alternative Parents

Substituents

Nitrogen mustard
Phosphoric monoester diamide
Organic phosphoric acid derivative
Oxazaphosphinane
Organic phosphoric acid amide
Azacycle
Organoheterocyclic compound
Alkanolamine
Oxacycle
Alkyl chloride
Organopnictogen compound
Organooxygen compound
Organochloride
Organohalogen compound
Organic oxygen compound
Alkyl halide
Hydrocarbon derivative
Organic oxide
Aliphatic heteromonocyclic compound

Molecular Framework

Aliphatic heteromonocyclic compounds

External Descriptors

organochlorine compound (CHEBI:1864 )
nitrogen mustard (CHEBI:1864 )
phosphorodiamide (CHEBI:1864 )

Ontology

Physiological effect

Not Available

Disposition

Biological location

Non-excretory biofluid

Biofluid or Excreta

Blood (PMID: 21059682)

Organ

Liver (HMDB: HMDB0013856)
Kidney (HMDB: HMDB0013856)

Excreta

Biofluid or Excreta

Urine (PMID: 21059682)

Cellular substructure

Extracellular (HMDB: HMDB0013856)

Source

Endogenous

Endogenous (HMDB: HMDB0013856)

Process

Naturally occurring process

Biological process

Biochemical pathway

Drug action pathway

Cyclophosphamide Action Pathway (PathBank: SMP0000447)

Metabolic pathway

Cyclophosphamide Metabolism Pathway (PathBank: SMP0000604)

Role

Not Available

Physical Properties

State

Not Available

Experimental Molecular Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Experimental Chromatographic Properties

Not Available

Predicted Molecular Properties

Property	Value	Source
Water Solubility	22.5 g/L	ALOGPS
logP	-0.02	ALOGPS
logP	-0.057	ChemAxon
logS	-1.1	ALOGPS
pKa (Strongest Acidic)	10.68	ChemAxon
pKa (Strongest Basic)	0.0052	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	61.8 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	59.09 m³·mol⁻¹	ChemAxon
Polarizability	24.57 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DeepCCS	[M+H]+	151.337	30932474
DeepCCS	[M-H]-	148.979	30932474
DeepCCS	[M-2H]-	183.898	30932474
DeepCCS	[M+Na]+	158.498	30932474
AllCCS	[M+H]+	155.7	32859911
AllCCS	[M+H-H2O]+	152.4	32859911
AllCCS	[M+NH4]+	158.8	32859911
AllCCS	[M+Na]+	159.7	32859911
AllCCS	[M-H]-	152.2	32859911
AllCCS	[M+Na-2H]-	153.2	32859911
AllCCS	[M+HCOO]-	154.3	32859911

Predicted Retention Times

Underivatized

Chromatographic Method	Retention Time	Reference
Measured using a Waters Acquity ultraperformance liquid chromatography (UPLC) ethylene-bridged hybrid (BEH) C18 column (100 mm × 2.1 mm; 1.7 μmparticle diameter). Predicted by Afia on May 17, 2022. Predicted by Afia on May 17, 2022.	3.96 minutes	32390414
Predicted by Siyang on May 30, 2022	11.2132 minutes	33406817
Predicted by Siyang using ReTip algorithm on June 8, 2022	2.05 minutes	32390414
AjsUoB = Accucore 150 Amide HILIC with 10mM Ammonium Formate, 0.1% Formic Acid	54.5 seconds	40023050
Fem_Long = Waters ACQUITY UPLC HSS T3 C18 with Water:MeOH and 0.1% Formic Acid	1388.6 seconds	40023050
Fem_Lipids = Ascentis Express C18 with (60:40 water:ACN):(90:10 IPA:ACN) and 10mM NH4COOH + 0.1% Formic Acid	292.6 seconds	40023050
Life_Old = Waters ACQUITY UPLC BEH C18 with Water:(20:80 acetone:ACN) and 0.1% Formic Acid	126.9 seconds	40023050
Life_New = RP Waters ACQUITY UPLC HSS T3 C18 with Water:(30:70 MeOH:ACN) and 0.1% Formic Acid	179.8 seconds	40023050
RIKEN = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	94.1 seconds	40023050
Eawag_XBridgeC18 = XBridge C18 3.5u 2.1x50 mm with Water:MeOH and 0.1% Formic Acid	362.0 seconds	40023050
BfG_NTS_RP1 =Agilent Zorbax Eclipse Plus C18 (2.1 mm x 150 mm, 3.5 um) with Water:ACN and 0.1% Formic Acid	363.7 seconds	40023050
HILIC_BDD_2 = Merck SeQuant ZIC-HILIC with ACN(0.1% formic acid):water(16 mM ammonium formate)	68.0 seconds	40023050
UniToyama_Atlantis = RP Waters Atlantis T3 (2.1 x 150 mm, 5 um) with ACN:Water and 0.1% Formic Acid	871.0 seconds	40023050
BDD_C18 = Hypersil Gold 1.9µm C18 with Water:ACN and 0.1% Formic Acid	365.4 seconds	40023050
UFZ_Phenomenex = Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex with Water:MeOH and 0.1% Formic Acid	1205.7 seconds	40023050
SNU_RIKEN_POS = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	279.4 seconds	40023050
RPMMFDA = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	318.0 seconds	40023050
MTBLS87 = Merck SeQuant ZIC-pHILIC column with ACN:Water and :ammonium carbonate	321.7 seconds	40023050
KI_GIAR_zic_HILIC_pH2_7 = Merck SeQuant ZIC-HILIC with ACN:Water and 0.1% FA	239.9 seconds	40023050
Meister zic-pHILIC pH9.3 = Merck SeQuant ZIC-pHILIC column with ACN:Water 5mM NH4Ac pH9.3 and 5mM ammonium acetate in water	16.1 seconds	40023050

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
4-Hydroxycyclophosphamide	OC1CCOP(=O)(N1)N(CCCl)CCCl	3050.5	Standard polar	33892256
4-Hydroxycyclophosphamide	OC1CCOP(=O)(N1)N(CCCl)CCCl	2041.6	Standard non polar	33892256
4-Hydroxycyclophosphamide	OC1CCOP(=O)(N1)N(CCCl)CCCl	2174.1	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
4-Hydroxycyclophosphamide,1TMS,isomer #1	C[Si](C)(C)OC1CCOP(=O)(N(CCCl)CCCl)N1	2109.0	Semi standard non polar	33892256
4-Hydroxycyclophosphamide,1TMS,isomer #2	C[Si](C)(C)N1C(O)CCOP1(=O)N(CCCl)CCCl	2151.1	Semi standard non polar	33892256
4-Hydroxycyclophosphamide,2TMS,isomer #1	C[Si](C)(C)OC1CCOP(=O)(N(CCCl)CCCl)N1[Si](C)(C)C	2175.2	Semi standard non polar	33892256
4-Hydroxycyclophosphamide,2TMS,isomer #1	C[Si](C)(C)OC1CCOP(=O)(N(CCCl)CCCl)N1[Si](C)(C)C	2098.7	Standard non polar	33892256
4-Hydroxycyclophosphamide,2TMS,isomer #1	C[Si](C)(C)OC1CCOP(=O)(N(CCCl)CCCl)N1[Si](C)(C)C	2676.9	Standard polar	33892256
4-Hydroxycyclophosphamide,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC1CCOP(=O)(N(CCCl)CCCl)N1	2348.0	Semi standard non polar	33892256
4-Hydroxycyclophosphamide,1TBDMS,isomer #2	CC(C)(C)[Si](C)(C)N1C(O)CCOP1(=O)N(CCCl)CCCl	2408.6	Semi standard non polar	33892256
4-Hydroxycyclophosphamide,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC1CCOP(=O)(N(CCCl)CCCl)N1[Si](C)(C)C(C)(C)C	2598.3	Semi standard non polar	33892256
4-Hydroxycyclophosphamide,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC1CCOP(=O)(N(CCCl)CCCl)N1[Si](C)(C)C(C)(C)C	2529.5	Standard non polar	33892256
4-Hydroxycyclophosphamide,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC1CCOP(=O)(N(CCCl)CCCl)N1[Si](C)(C)C(C)(C)C	2844.2	Standard polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxycyclophosphamide GC-MS (Non-derivatized) - 70eV, Positive	splash10-02bu-5890000000-a427d5c4bf9209482b43	2017-09-01	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxycyclophosphamide GC-MS (1 TMS) - 70eV, Positive	splash10-05g1-7392000000-4b076778aadb22b57ed1	2017-10-06	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxycyclophosphamide GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	Wishart Lab	View Spectrum

MS/MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 10V, Positive-QTOF	splash10-0a6r-8290000000-b01da8a61b60048b29f7	2016-08-02	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 20V, Positive-QTOF	splash10-002f-9800000000-70f292b6f3c854cf93a2	2016-08-02	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 40V, Positive-QTOF	splash10-0a6u-9000000000-c8f75a918284b672a062	2016-08-02	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 10V, Negative-QTOF	splash10-03fr-1790000000-e9e004489e6cc1b1144d	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 20V, Negative-QTOF	splash10-00di-9000000000-9b317f1b0c85a67d882e	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 40V, Negative-QTOF	splash10-0007-9000000000-21ced355676eb4ed7c49	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 10V, Negative-QTOF	splash10-004i-0090000000-6c1af332aad878673a4b	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 20V, Negative-QTOF	splash10-004i-1290000000-097d11cc59c075d92e8e	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 40V, Negative-QTOF	splash10-01u0-9100000000-358d49458e7399802e5d	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 10V, Positive-QTOF	splash10-004i-0090000000-312fa45820b98bd8a809	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 20V, Positive-QTOF	splash10-004i-3790000000-737d73cd2cdf34a3c57e	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxycyclophosphamide 40V, Positive-QTOF	splash10-0a4l-9520000000-a847f1236ae0f8522c8a	2021-09-24	Wishart Lab	View Spectrum

Biological Properties

Cellular Locations

Extracellular

Biospecimen Locations

Blood
Urine

Tissue Locations

Kidney
Liver

Pathways

Name	SMPDB/PathBank	KEGG
Cyclophosphamide Action Pathway		Not Available
Cyclophosphamide Metabolism Pathway		Not Available

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry	21059682	details
Urine	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry	21059682	details

Abnormal Concentrations

Not Available

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

Not Available

KEGG Compound ID

C07643

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

4-Hydroxycyclophosphamide

METLIN ID

Not Available

PubChem Compound

99735

PDB ID

Not Available

ChEBI ID

1864

Food Biomarker Ontology

Not Available

VMH ID

Not Available

MarkerDB ID

Not Available

Good Scents ID

Not Available

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Not Available

General References

Griskevicius L, Meurling L, Hassan M: Simple method based on fluorescent detection for the determination of 4-hydroxycyclophosphamide in plasma. Ther Drug Monit. 2002 Jun;24(3):405-9. doi: 10.1097/00007691-200206000-00013. [PubMed:12021633 ]
Low JE, Borch RF, Sladek NE: Conversion of 4-hydroperoxycyclophosphamide and 4-hydroxycyclophosphamide to phosphoramide mustard and acrolein mediated by bifunctional catalysis. Cancer Res. 1982 Mar;42(3):830-7. [PubMed:7059981 ]
Raccor BS, Claessens AJ, Dinh JC, Park JR, Hawkins DS, Thomas SS, Makar KW, McCune JS, Totah RA: Potential contribution of cytochrome P450 2B6 to hepatic 4-hydroxycyclophosphamide formation in vitro and in vivo. Drug Metab Dispos. 2012 Jan;40(1):54-63. doi: 10.1124/dmd.111.039347. Epub 2011 Oct 5. [PubMed:21976622 ]

Enzymes

Enzyme Details

1. Cytochrome P450 3A4

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:: CYP3A4
Uniprot ID:: P08684
Molecular weight:: 57255.585

References

Enzyme Details

2. Cytochrome P450 2C9

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:: CYP2C9
Uniprot ID:: P11712
Molecular weight:: 55627.365

References

Enzyme Details

3. Cytochrome P450 2C19

General function:: Involved in monooxygenase activity
Specific function:: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:: CYP2C19
Uniprot ID:: P33261
Molecular weight:: 55944.565

References

Enzyme Details

4. Cytochrome P450 2D6

General function:: Involved in monooxygenase activity
Specific function:: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:: CYP2D6
Uniprot ID:: P10635
Molecular weight:: 55768.94

References

Enzyme Details

5. Cytochrome P450 2C18

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:: CYP2C18
Uniprot ID:: P33260
Molecular weight:: 55710.075

References

Enzyme Details

6. Cytochrome P450 2B6

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:: CYP2B6
Uniprot ID:: P20813
Molecular weight:: 56277.81

References

Enzyme Details

7. Cytochrome P450 3A7

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:: CYP3A7
Uniprot ID:: P24462
Molecular weight:: 57525.03

References

Enzyme Details

8. Cytochrome P450 2C8

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:: CYP2C8
Uniprot ID:: P10632
Molecular weight:: 55824.275

References

Enzyme Details

9. Cytochrome P450 2A6

General function:: Involved in monooxygenase activity
Specific function:: Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:: CYP2A6
Uniprot ID:: P11509
Molecular weight:: 56517.005

References

Transporters

Enzyme Details

1. Multidrug resistance protein 1

General function:: Involved in ATP binding
Specific function:: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:: ABCB1
Uniprot ID:: P08183
Molecular weight:: 141477.3

References

Showing metabocard for 4-Hydroxycyclophosphamide (HMDB0013856)

MOL for HMDB0013856 (4-Hydroxycyclophosphamide)

3D MOL for HMDB0013856 (4-Hydroxycyclophosphamide)

3D SDF for HMDB0013856 (4-Hydroxycyclophosphamide)

3D-SDF for HMDB0013856 (4-Hydroxycyclophosphamide)

PDB for HMDB0013856 (4-Hydroxycyclophosphamide)

3D PDB for HMDB0013856 (4-Hydroxycyclophosphamide)

SMILES for HMDB0013856 (4-Hydroxycyclophosphamide)

INCHI for HMDB0013856 (4-Hydroxycyclophosphamide)

Structure for HMDB0013856 (4-Hydroxycyclophosphamide)

3D Structure for HMDB0013856 (4-Hydroxycyclophosphamide)

Predicted Collision Cross Sections

Predicted Retention Times

Underivatized

Predicted Kovats Retention Indices

Underivatized

Derivatized

GC-MS Spectra

MS/MS Spectra

Enzymes

References

References

References

References

References

References

References

References

References

Transporters

References