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Identification
Name Cyclophosphamide
Accession Number DB00531 (APRD00408)
Type small molecule
Groups approved
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. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
ASTA
Asta B 518
Clafen
Claphene
CY
Cyclophosphamid
Cyclophosphamide Monohydrate
Cyclophosphamide Sterile
Cyclophosphamidum
Cyclophosphan
Cyclophosphane
Cyclophosphoramide
Cyclostin
Cyklofosfamid
Cytophosphan
Cytoxan
Cytoxan Lyoph
Endoxan
Endoxan R
Endoxan-Asta
Endoxana
Endoxanal
Endoxane
Enduxan
Genoxal
Hexadrin
Lyophilized Cytoxan
Mitoxan
Neosar
Procytox
Rcra Waste Number U058
Revimmune
Semdoxan
Sendoxan
Senduxan
Zyklophosphamid
First Prev Next Last
Brand mixtures
Brand Name Ingredients
Procytox for Injection 2000mg Pws Iv Cyclophosphamide + Sodium Chloride
Categories
  • Antineoplastic Agents
  • Antirheumatic Agents
  • Immunosuppressive Agents
  • Antineoplastic Agents, Alkylating
  • Myeloablative Agonists
  • Mutagens
CAS number 6055-19-2
Weight Average: 261.086
Monoisotopic: 260.02481966
Chemical Formula C7H15Cl2N2O2P
InChI Key InChIKey=CMSMOCZEIVJLDB-UHFFFAOYSA-N
InChI
InChI=1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)
Plain Text
IUPAC Name
2-[bis(2-chloroethyl)amino]-1,3,2$l^{5}-oxazaphosphinan-2-one
SMILES
ClCCN(CCCl)P1(=O)NCCCO1
Plain Text
Mass Spec show (9.91 KB)
Taxonomy
Kingdom Organic
Classes
  • Nitrogen Mustards
Substructures
  • Organophosphate Esters
  • Phosphoric Acids and Derivatives
  • Alkyl Halides
  • Heterocyclic compounds
  • Nitrogen Mustards
Pharmacology
Indication For management of malignant lymphomas, multiple myeloma,leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma and carcinoma of the breast
Pharmacodynamics Cyclophosphamide is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
Mechanism of action 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.
Absorption 90-100%
Volume of distribution Not Available
Protein binding >60%
Metabolism
hepatic

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Cyclophosphamide
4-Hydroxycyclophosphamide Details
Cyclophosphamide
Dechloroethyl cyclophosphamide Details
Cyclophosphamide
    		Aldophosphamide Details
    Route of elimination It is eliminated primarily in the form of metabolites, but from 5% to 25% of the dose is excreted in urine as unchanged drug.
    Half life 3-12 hours
    Clearance Not Available
    Toxicity infection, myelosuppression, and cardiac toxicity
    Affected organisms
    • Humans and other mammals
    Pathways
    Pathway Name SMPDB ID
    Smp00447 Cyclophosphamide Pathway SMP00447
    Pharmacoeconomics
    Manufacturers
    • Baxter healthcare corp
    • Baxter healthcare corp anesthesia and critical care
    • Teva parenteral medicines inc
    • Roxane laboratories inc
    Packagers
    Dosage forms
    Form Route Strength
    Powder, for solution Intravenous
    Solution Intravenous
    Tablet Oral
    Prices
    Unit description Cost Unit
    Cyclophosphamide 500 mg vial 37.76 USD vial
    Cyclophosphamide 100% powder 33.66 USD g
    Cytoxan 500 mg vial 15.25 USD vial
    Cytoxan 50 mg tablet 4.14 USD tablet
    Cyclophosphamide 50 mg tablet 3.92 USD tablet
    Cytoxan 25 mg tablet 2.26 USD tablet
    Cyclophosphamide 25 mg tablet 2.09 USD tablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    Patents Not Available
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 41-45 °C Not Available
    water solubility Soluble. 1-5 g/100 mL at 23 °C Not Available
    logP 0.8 Not Available
    Predicted Properties
    Property Value Source
    water solubility 1.51e+01 g/l ALOGPS
    logP 0.76 ALOGPS
    logP 0.097 ChemAxon
    logS -1.2 ALOGPS
    pKa (strongest acidic) 12.78 ChemAxon
    pKa (strongest basic) -0.57 ChemAxon
    physiological charge 0 ChemAxon
    hydrogen acceptor count 2 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 41.57 ChemAxon
    rotatable bond count 5 ChemAxon
    refractivity 58.48 ChemAxon
    polarizability 23.72 ChemAxon
    References
    Synthesis Reference Not Available
    General Reference
    1. Brock N: The history of the oxazaphosphorine cytostatics. Cancer. 1996 Aug 1;78(3):542-7. Pubmed
    2. Brock N: Oxazaphosphorine cytostatics: past-present-future. Seventh Cain Memorial Award lecture. Cancer Res. 1989 Jan 1;49(1):1-7. Pubmed
    External Links
    Resource Link
    KEGG Drug D00287 Link_out
    PubChem Compound 2907 Link_out
    PubChem Substance 46505441 Link_out
    ChemSpider 2804 Link_out
    ChEBI 4027 Link_out
    ChEMBL 4027 Link_out
    Therapeutic Targets Database DAP000532 Link_out
    PharmGKB PA449165 Link_out
    Drug Product Database 2241797 Link_out
    RxList http://www.rxlist.com/cgi/generic3/cyclophosphamide.htm Link_out
    Drugs.com http://www.drugs.com/cdi/cyclophosphamide.html Link_out
    PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cyt1112.shtml Link_out
    Wikipedia http://en.wikipedia.org/wiki/Cyclophosphamide Link_out
    ATC Codes
    • L01AA01
    • L01DB07
    AHFS Codes
    • 10:00.00
    PDB Entries Not Available
    FDA label Not Available
    MSDS show (76.1 KB)
    Interactions
    Drug Interactions
    Drug Interaction
    Acenocoumarol The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of acenocoumarol.
    Anisindione The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of anisindione.
    Bendamustine Increases toxicity through pharmacodynamic synergism. Additive myelosuppression.
    Dicumarol The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of dicumarol.
    Digoxin The antineoplasic agent decreases the effect of digoxin
    Fluconazole Fluconazole reduces metabolism and clearance of cyclophosphamide.
    Pentostatin Increased toxicity of cyclophosphamide
    Succinylcholine Cyclophosphamide may increase the effect of succinylcholine.
    Thiotepa Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Cyclophosphamide, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Cyclophosphamide if Thiotepa is initiated, discontinued or dose changed.
    Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
    Warfarin The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of warfarin.
    Food Interactions
    • Drink liberally- 2 to 3 liters/day.
    • Take with food to reduce irritation.
    Targets

    1. DNA

    Pharmacological action: yes
    Actions: cross-linking/alkylation

    DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

    Gene Sequence: FASTA

    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
    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
    3. Khan O, Middleton MR: The therapeutic potential of O6-alkylguanine DNA alkyltransferase inhibitors. Expert Opin Investig Drugs. 2007 Oct;16(10):1573-84. Pubmed
    4. Schmidt E, Tony HP, Brocker EB, Kneitz C: Sun-induced life-threatening lupus nephritis. Ann N Y Acad Sci. 2007 Jun;1108:35-40. Pubmed
    5. Zhang QH, Wu CF, Duan L, Yang JY: Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells. Food Chem Toxicol. 2007 Aug 23;. Pubmed
    Enzymes

    1. Cytochrome P450 2C9

    Actions: substrate, inducer

    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

    UniProt ID: P11712 Link_out
    Gene: CYP2C9
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
    2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    2. Cytochrome P450 3A4

    Actions: substrate, inhibitor, inducer

    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. The enzyme also hydroxylates etoposide

    UniProt ID: P08684 Link_out
    Gene: CYP3A4
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
    2. Preiss R, Schmidt R, Baumann F, Hanschmann H, Hauss J, Geissler F, Pahlig H, Ratzewiss B: Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. J Cancer Res Clin Oncol. 2002 Jul;128(7):385-92. Epub 2002 Jun 11. Pubmed
    3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    3. Cytochrome P450 2B6

    Actions: substrate, inducer

    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

    UniProt ID: P20813 Link_out
    Gene: CYP2B6 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
    2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
    3. Preiss R, Schmidt R, Baumann F, Hanschmann H, Hauss J, Geissler F, Pahlig H, Ratzewiss B: Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. J Cancer Res Clin Oncol. 2002 Jul;128(7):385-92. Epub 2002 Jun 11. Pubmed
    4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    4. Cytochrome P450 2C19

    Actions: substrate

    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

    UniProt ID: P33261 Link_out
    Gene: CYP2C19 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
    2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    5. Cytochrome P450 2A6

    Actions: substrate

    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

    UniProt ID: P11509 Link_out
    Gene: CYP2A6
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    6. Cytochrome P450 2C18

    Actions: substrate

    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

    UniProt ID: P33260 Link_out
    Gene: CYP2C18 Link_out
    Protein Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    7. Cytochrome P450 2C8

    Actions: substrate, inducer

    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)

    UniProt ID: P10632 Link_out
    Gene: CYP2C8
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    8. Cytochrome P450 2D6

    Actions: substrate

    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

    UniProt ID: P10635 Link_out
    Gene: CYP2D6 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    9. Cytochrome P450 3A7

    Actions: substrate

    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

    UniProt ID: P24462 Link_out
    Gene: CYP3A7 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
    Transporters

    1. Multidrug resistance protein 1

    Actions: inhibitor

    Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

    UniProt ID: P08183 Link_out
    Gene: ABCB1 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    References:
    1. Wang E, Lew K, Barecki M, Casciano CN, Clement RP, Johnson WW: Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4. Chem Res Toxicol. 2001 Dec;14(12):1596-603. Pubmed
    Comments
    Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19