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Showing drug card for Busulfan (DB01008)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:20
Primary Accession Number DB01008
Secondary Accession Number
  • APRD00664
Name Busulfan
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description An alkylating agent having a selective immunosuppressive effect on bone marrow. It has been used in the palliative treatment of chronic myeloid leukemia (myeloid leukemia, chronic), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen. [PubChem]
Synonyms
  1. Busulphan
  2. Busulphane
  3. Butanedioldimethanesulfonate
  4. Buzulfan
  5. Sulfabutin
  6. Sulphabutin
  7. Tetramethylene Dimethane Sulfonate
  8. Tetramethylenester Kyseliny Methansulfonove
  9. busulfan
Brand Names
  1. Busulfex
  2. Citosulfan
  3. Leucosulfan
  4. Mablin
  5. Mielevcin
  6. Mielosan
  7. Mielucin
  8. Milecitan
  9. Mileran
  10. Misulban
  11. Mitosan
  12. Mitostan
  13. Myeleukon
  14. Myeloleukon
  15. Myelosan
  16. Mylecytan
  17. Myleran
  18. Myleran Tablets
Brand Mixtures Not Available
Chemical IUPAC Name 4-methylsulfonyloxybutyl methanesulfonate
Chemical Formula C6H14O6S2
Chemical Structure Structure
CAS Registry Number 55-98-1
InChI Identifier InChI=1/C6H14O6S2/c1-13(7,8)11-5-3-4-6-12-14(2,9)10/h3-6H2,1-2H3
InChI Key COVZYZSDYWQREU-UHFFFAOYAO
KEGG Drug D00248 Link Image
KEGG Compound Not Available
PubChem Compound 2478 Link Image
PubChem Substance 148760 Link Image
ChEBI ID Not Available
PharmGKB ID PA448691 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02240602 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/busulfan.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Busulfan Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference U.S. pat. 2,917,432(1959)
Average Molecular Weight 246.3020
Monoisotopic Molecular Weight 246.0232
State Solid
Melting Point 287 oC
Experimental Water Solubility 6.9E+004 mg/L Source: PhysProp
Predicted Water Solubility 5.16e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -0.3 Source: PhysProp
Predicted LogP -0.89 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.68 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 CS(=O)(=O)OCCCCOS(C)(=O)=O
Canonical SMILES CS(=O)(=O)OCCCCOS(C)(=O)=O
Drug Category
  • Alkylating Agents
  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Immunosuppressive Agents
  • Myeloablative Agonists
ATC Codes
AHFS Codes
  • 10:00.00
Indication For use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.
Pharmacology Busulfan 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 Completely absorbed from the gastrointestinal tract.
Toxicity Signs of overdose include allergic reaction, unusual bleeding or bruising, sudden weakness or unusual fatigue, persistent cough, congestion, or shortness of breath; flank, stomach or joint pain; pronounced nausea, vomiting, diarrhea, dizziness, confusion, or darkening of the skin, chills, fever, collapse, and loss of consciousness.
Protein Binding 32.4%
Biotransformation Mainly Hepatic. Busulfan is predominantly metabolized by conjugation with glutathione, both spontaneously and by glutathione S-transferase (GST) catalysis.
Half Life 2.5 hours
Dosage Forms
Form Route
Solution Intravenous
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Metronidazole Metronidazole increases the effect/toxicity of busulfan
Food Interactions
  • Drink liberally.
  • Take without regard to meals.
Pathways Not Available
General References
  1. Lesurtel M, Graf R, Aleil B, Walther DJ, Tian Y, Jochum W, Gachet C, Bader M, Clavien PA: Platelet-derived serotonin mediates liver regeneration. Science. 2006 Apr 7;312(5770):104-7. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
  4. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
  2. Glutathione S-transferase A1
  3. Glutathione S-transferase A2
Targets
  1. DNA
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Glutathione S-transferase A1
Enzyme 2 Gene Name GSTA1
Enzyme 2 SwissProt ID P08263 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P08263|GSTA1_HUMAN Glutathione S-transferase A1 
AEKPKLHYFNARGRMESTRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEID
GMKLVQTRAILNYIASKYNLYGKDIKERALIDMYIEGIADLGEMILLLPVCPPEEKDAKL
ALIKEKIKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPLL
KALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEEARKIFRF
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Glutathione S-transferase A2
Enzyme 3 Gene Name GSTA2
Enzyme 3 SwissProt ID P09210 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 Protein Sequence >sp|P09210|GSTA2_HUMAN Glutathione S-transferase A2 
AEKPKLHYSNIRGRMESIRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEID
GMKLVQTRAILNYIASKYNLYGKDIKEKALIDMYIEGIADLGEMILLLPFTQPEEQDAKL
ALIQEKTKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPLL
KALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEESRKIFRF
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. Morales-Ramirez P, Gonzalez-Beltran F: Different behavior of SCE-eliciting lesions induced by low and high doses of busulfan. Environ Mol Mutagen. 2007 Sep 26;48(8):706-714. [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.