| 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 |
|
| 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 |
- Busulphan
- Busulphane
- Butanedioldimethanesulfonate
- Buzulfan
- Sulfabutin
- Sulphabutin
- Tetramethylene Dimethane Sulfonate
- Tetramethylenester Kyseliny Methansulfonove
- busulfan
|
| Brand Names |
- Busulfex
- Citosulfan
- Leucosulfan
- Mablin
- Mielevcin
- Mielosan
- Mielucin
- Milecitan
- Mileran
- Misulban
- Mitosan
- Mitostan
- Myeleukon
- Myeloleukon
- Myelosan
- Mylecytan
- Myleran
- Myleran Tablets
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
4-methylsulfonyloxybutyl methanesulfonate |
| Chemical Formula |
C6H14O6S2 |
| Chemical 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  |
| KEGG Compound |
Not Available |
| PubChem Compound |
2478  |
| PubChem Substance |
148760  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA448691  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02240602  |
| RxList Link |
http://www.rxlist.com/cgi/generic2/busulfan.htm  |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Busulfan  |
| 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 | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 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 |
|
| 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  |
| Contraindications |
Show  |
| Interactions |
Show  |
| 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 |
- 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
]
- Drugs.com

- Wikipedia

- RxList

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 3A4 (CYP3A4)
- Glutathione S-transferase A1
- Glutathione S-transferase A2
|
| Targets |
- DNA
|
|
Drug Target 1
[top]
|
| Target 1 ID |
874 |
| Target 1 Name |
DNA |
| Target 1 Synonyms |
- 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 |
|
| 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 |
|
| Target 1 Transmembrane Regions |
|
| 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  |
| Target 1 PDB File |
Show |
| Target 1 3D Structure |
|
| Target 1 Cellular Location |
|
| 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 |
- 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
]
|
| Target 1 Drug References |
- 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
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
- 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
]
|