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Showing drug card for Cyclophosphamide (DB00531)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:08:24
Primary Accession Number DB00531
Secondary Accession Number
  • APRD00408
Name Cyclophosphamide
Drug Type
  • Approved
  • Investigational
  • 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. [PubChem]
Synonyms
  1. cyclophosphamide
Brand Names
  1. ASTA
  2. Asta B 518
  3. CP
  4. CPA
  5. CTX
  6. CY
  7. Clafen
  8. Claphene
  9. Cyclophosphamid
  10. Cyclophosphamide Monohydrate
  11. Cyclophosphamide Sterile
  12. Cyclophosphamidum
  13. Cyclophosphan
  14. Cyclophosphane
  15. Cyclophosphoramide
  16. Cyclostin
  17. Cyklofosfamid
  18. Cytophosphan
  19. Cytoxan
  20. Cytoxan Lyoph
  21. Endoxan
  22. Endoxan R
  23. Endoxan-Asta
  24. Endoxana
  25. Endoxanal
  26. Endoxane
  27. Enduxan
  28. Genoxal
  29. Hexadrin
  30. Lyophilized Cytoxan
  31. Mitoxan
  32. Neosar
  33. Procytox
  34. Rcra Waste Number U058
  35. Revimmune
  36. Semdoxan
  37. Sendoxan
  38. Senduxan
  39. Zyklophosphamid
Brand Mixtures
  1. Procytox for Injection 2000mg Pws Iv (Cyclophosphamide + Sodium Chloride)
Chemical IUPAC Name N,N-bis(2-chloroethyl)-2-oxo-1-oxa-3-aza-2$l^{5}-phosphacyclohexan-2-amine
Chemical Formula C7H15Cl2N2O2P
Chemical Structure Structure
CAS Registry Number 6055-19-2
InChI Identifier InChI=1/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)/f/h10H
InChI Key CMSMOCZEIVJLDB-KZFATGLACB
KEGG Drug D00287 Link Image
KEGG Compound Not Available
PubChem Compound 2907 Link Image
PubChem Substance 148529 Link Image
ChEBI ID Not Available
PharmGKB ID PA449165 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02241797 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/cyclophosphamide.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cyt1112.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Cyclophosphamide Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Arnold et al, Angew.Chem., 70; 539; 543(1958)
Average Molecular Weight 261.0860
Monoisotopic Molecular Weight 260.0248
State Solid
Melting Point 41-45 oC
Experimental Water Solubility Soluble. 1-5 g/100 mL at 23 oC Source: PhysProp
Predicted Water Solubility 1.51e+01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 0.8 Source: PhysProp
Predicted LogP 0.76 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.24 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES ClCCN(CCCl)[P@]1(=O)NCCCO1
Canonical SMILES ClCCN(CCCl)P1(=O)NCCCO1
Drug Category
  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Antirheumatic Agents
  • Immunosuppressive Agents
  • Mutagens
  • Myeloablative Agonists
ATC Codes
AHFS Codes
  • 10:00.00
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
Pharmacology 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%
Toxicity infection, myelosuppression, and cardiac toxicity
Protein Binding >60%
Biotransformation hepatic
Half Life 3-12 hours
Dosage Forms
Form Route
Powder, for solution Intravenous
Solution Intravenous
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Increases the anticoagulant effect
Anisindione Increases the anticoagulant effect
Dicumarol Increases the anticoagulant effect
Digoxin The antineoplasic agent decreases the effect of digoxin
Fluconazole Fluconazole reduces metabolism and clearance of cyclophosphamide
Pentostatin Increased toxicity of cyclophosphamide
Succinylcholine The agent increases the effect of succinylcholine
Warfarin Increases the anticoagulant effect
Food Interactions
  • Drink liberally- 2 to 3 liters/day.
  • Take with food to reduce irritation.
Pathways Not Available
General References
  1. Brock N: Oxazaphosphorine cytostatics: past-present-future. Seventh Cain Memorial Award lecture. Cancer Res. 1989 Jan 1;49(1):1-7. [PubMed Link Image]
  2. Brock N: The history of the oxazaphosphorine cytostatics. Cancer. 1996 Aug 1;78(3):542-7. [PubMed Link Image]
  3. Drugs.com Link Image
  4. Wikipedia Link Image
  5. RxList Link Image
  6. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2B6 (CYP2B6)
Targets
  1. DNA
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2B6 (CYP2B6)
Enzyme 1 Gene Name CYP2B6
Enzyme 1 SwissProt ID P20813 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P20813|CP2B6_HUMAN Cytochrome P450 2B6 (EC 1.14.14.1) 
MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRGLLKSFLRFRE
KYGDVFTVHLGPRPVVMLCGVEAIREALVDKAEAFSGRGKIAMVDPFFRGYGVIFANGNR
WKVLRRFSVTTMRDFGMGKRSVEERIQEEAQCLIEELRKSKGALMDPTFLFQSITANIIC
SIVFGKRFHYQDQEFLKMLNLFYQTFSLISSVFGQLFELFSGFLKYFPGAHRQVYKNLQE
INAYIGHSVEKHRETLDPSAPKDLIDTYLLHMEKEKSNAHSEFSHQNLNLNTLSLFFAGT
ETTSTTLRYGFLLMLKYPHVAERVYREIEQVIGPHRPPELHDRAKMPYTEAVIYEIQRFS
DLLPMGVPHIVTQHTSFRGYIIPKDTEVFLILSTALHDPHYFEKPDAFNPDHFLDANGAL
KKTEAFIPFSLGKRICLGEGIARAELFLFFTTILQNFSMASPVAPEDIDLTPQECGVGKI
PPTYQIRFLPR
Drug Target 1 [top]
Target 1 ID 874
Target 1 Name DNA
Target 1 Synonyms
  1. Deoxyribonucleic acid
Target 1 Gene Name Not Available
Target 1 Protein Sequence Not Available
Target 1 Number of Residues 0
Target 1 Molecular Weight 7656 (double strand)
Target 1 Theoretical pI Not Available
Target 1 GO Classification
Function
information storage
information transfer
Process
DNA replication and chromosomal cycle
DNA replication
DNA-dependent DNA replication
DNA replication, synthesis of RNA primer
transcription
transcription, DNA dependent
Component
cell
intracellular
nucleus
mitochondria
Target 1 General Function Biological information storage and information transfer
Target 1 Specific Function 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.
Target 1 Pathways
Name SMPDB Link KEGG Link
DNA polymerase map03030 Link Image
RNA polymerase map03020 Link Image
Target 1 Reactions
  • DNA + DNA polymerase + nNTP = 2 DNA + nNDP; DNA + RNA polymerase + NTP = mRNA + nNDP
Target 1 Pfam Domain Function Not Available
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein Not Available
Target 1 UniProtKB/Swiss-Prot ID Not Available
Target 1 UniProtKB/Swiss-Prot Entry Name Not Available
Target 1 PDB ID 1BNA Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Nucleus and mitochondria
Target 1 Gene Sequence >Example: Dickerson dodecamer 
CGCGAATTCGCG
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus All loci
Target 1 SNPs Not Available
Target 1 General References
  1. Nadeau D, Marchand C: Change in the kinetics of sulphacetamide tissue distribution in Walker tumor-bearing rats. Drug Metab Dispos. 1975 Nov-Dec;3(6):565-76. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
  3. 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 Link Image]
  4. 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 Link Image]
  5. Khan O, Middleton MR: The therapeutic potential of O6-alkylguanine DNA alkyltransferase inhibitors. Expert Opin Investig Drugs. 2007 Oct;16(10):1573-84. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.