ContaminantDB: Cyclophosphamide

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (1)XML

Record Information

Version

1.0

Creation Date

2014-09-11 05:13:41 UTC

Update Date

2026-05-21 16:37:05 UTC

Accession Number

CHEM003685

Identification

Common Name

Cyclophosphamide

Class

Small Molecule

Description

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.

Contaminant Sources

T3DB toxins

Contaminant Type

Amide
Antineoplastic Agent, Alkylating
Antirheumatic Agent
Drug
Ester
Immunosuppressive Agent
Mutagen
Myeloablative Agonist
Organic Compound
Organochloride
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(+-)-Cyclophosphamide	ChEBI
(RS)-Cyclophosphamide	ChEBI
2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide	ChEBI
Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester	ChEBI
Cyclophosphamide anhydrous	ChEBI
N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide	ChEBI
Cytoxan	Kegg
Cyclophosphamide monohydrate	HMDB
Cytophosphan	HMDB
Sendoxan	HMDB
Anhydrous, cyclophosphamide	HMDB
Cyclophosphamide, (S)-isomer	HMDB
Cyclophosphane	HMDB
Cytophosphane	HMDB
Endoxan	HMDB
Neosar	HMDB
Cyclophosphamide, (R)-isomer	HMDB
Monohydrate, cyclophosphamide	HMDB
Procytox	HMDB
(+,-)-2-(Bis(2-chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate	HMDB

Chemical Formula

C₇H₁₅Cl₂N₂O₂P

Average Molecular Mass

261.086 g/mol

Monoisotopic Mass

260.025 g/mol

CAS Registry Number

Not Available

IUPAC Name

Not Available

Traditional Name

2-[bis(2-chloroethyl)amino]-1,3,2lambda5-oxazaphosphinan-2-one

SMILES

ClCCN(CCCl)P1(=O)NCCCO1

InChI Identifier

InChI=1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)

InChI Key

CMSMOCZEIVJLDB-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
Oxacycle
Organoheterocyclic compound
Azacycle
Hydrocarbon derivative
Organic oxide
Organooxygen compound
Organochloride
Organopnictogen compound
Organohalogen compound
Organic oxygen compound
Alkyl chloride
Alkyl halide
Aliphatic heteromonocyclic compound

Molecular Framework

Aliphatic heteromonocyclic compounds

External Descriptors

organochlorine compound (CHEBI:4027 )
nitrogen mustard (CHEBI:4027 )
phosphorodiamide (CHEBI:4027 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	48-49°C
Boiling Point	Not Available
Solubility	Soluble. 1-5 g/100 mL at 23°C

Predicted Properties

Property	Value	Source
Water Solubility	15.1 g/L	ALOGPS
logP	0.76	ALOGPS
logP	0.097	ChemAxon
logS	-1.2	ALOGPS
pKa (Strongest Acidic)	13.43	ChemAxon
pKa (Strongest Basic)	0.084	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	41.57 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	58.48 m³·mol⁻¹	ChemAxon
Polarizability	23.72 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00dj-2930000000-a5e2529d99bd261703f0	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0059-1490000000-36d8ebdb421248c38c7b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-03di-1390000000-b8dc1a824ec33e388213	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-03di-0390000000-66983035d1db7ac36bd6	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-001l-0970000000-939110a705ed71803ab8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-0090000000-2bdfe4296c2bdf8d4a99	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-0190000000-1e8e017f8e39fa5d73cf	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0930000000-d7459c8d20a8fc59f6f0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0900000000-33cb20e845200f9d2618	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-2900000000-09d33a8387b9d152f24a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-01ox-6900000000-cdebe09ff6df7c25b477	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-0090000000-d749f27c3144da2c431c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-0190000000-a6fa921df18384671a7c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0930000000-abdb40162fc8a44200f7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0900000000-8c0705ee62a5f9c7d44e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-2900000000-a299026342c77e92c48c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-01ox-6900000000-fc2845c75bbccc83ad99	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-001l-0970000000-83e0f5b88b6fbe0a1ea7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0900000000-5490a2b493bfde967fa3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0900000000-456626f46e480e0ac670	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0006-9150000000-28408c9f0486cc7568f2	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-052f-9600000000-fd85ba5646421fb4dd68	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9100000000-dc67f093f2419f82cb18	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-1920000000-ef90686fe8c9da71ccd6	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-9000000000-c974342f3a086d037df6	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-002u-9600000000-142aeef910da3ef2f6b3	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-08fr-9470000000-53f4a8ff83c415492e03	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

After oral administration, peak concentrations occur at one hour.

Mechanism of Toxicity

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

Metabolism

Metabolism and activation occurs at the liver. 75% of the drug is activated by cytochrome P450 isoforms, CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18, and 2C19. The CYP2B6 isoform is the enzyme with the highest 4-hydroxylase activity. Cyclophosphamide undergoes activation to eventually form active metabolites, phosphoramide mustard and acrolein. Cyclophosphamide appears to induce its own metabolism which results in an overall increase in clearance, increased formation of 4-hydroxyl metabolites, and shortened t1/2 values following repeated administration.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

1, carcinogenic to humans. (3)

Uses/Sources

Cyclophosphamide is indicated for the treatment of malignant lymphomas, multiple myeloma, leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma, and carcinoma of the breast. It is also indicated for the treatment of biopsy-proven minimal change nephrotic syndrome in pediatric patients.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

DB00531

HMDB ID

HMDB0014672

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Riccardo Dalla-Favera, Alessandro Massimo Gianni, “Retroviral vector capable of transducing the aldehyde dehydrogenase-1 gene and making cells resistant to the chemotherapeutic agent cyclophosphamide and its derivatives and analogs.” U.S. Patent US6268138, issued March, 1999.

MSDS

Not Available

General References

1. https://www.ncbi.nlm.nih.gov/pubmed/?term=15711186

2. https://www.ncbi.nlm.nih.gov/pubmed/?term=7850793

3. Brock N: Oxazaphosphorine cytostatics: past-present-future. Seventh Cain Memorial Award lecture. Cancer Res. 1989 Jan 1;49(1):1-7.

4. Brock N: The history of the oxazaphosphorine cytostatics. Cancer. 1996 Aug 1;78(3):542-7.

5. FDA label

Cyclophosphamide (CHEM003685)

Structure for CHEM003685: Cyclophosphamide