ContaminantDB: Busulfan

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (2)XML

Record Information

Version

1.0

Creation Date

2014-09-11 05:14:45 UTC

Update Date

2026-03-31 18:38:19 UTC

Accession Number

CHEM003707

Identification

Common Name

Busulfan

Class

Small Molecule

Description

Busulfan is a bifunctional alkylating agent, having a selective immunosuppressive effect on bone marrow. It is not a structural analog of the nitrogen mustards. 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.

Contaminant Sources

HMDB Contaminants - Urine
HPV EPA Chemicals
IARC Carcinogens General
IARC Carcinogens Group 1
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Alkylating Agent
Antineoplastic Agent, Alkylating
Drug
Immunosuppressive Agent
Metabolite
Myeloablative Agonist
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
1,4-Bis(methanesulfonoxy)butane	ChEBI
1,4-Butanediol dimethanesulfonate	ChEBI
1,4-Dimesyloxybutane	ChEBI
1,4-Dimethanesulfonoxybutane	ChEBI
Bisulfex	ChEBI
Busulfano	ChEBI
Busulfanum	ChEBI
Leucosulfan	ChEBI
Mablin	ChEBI
Mielucin	ChEBI
Misulban	ChEBI
Mitostan	ChEBI
Myeloleukon	ChEBI
Myleran	ChEBI
Tetramethylene bis(methanesulfonate)	ChEBI
1,4-Bis(methanesulphonoxy)butane	Generator
1,4-Butanediol dimethanesulfonic acid	Generator
1,4-Butanediol dimethanesulphonate	Generator
1,4-Butanediol dimethanesulphonic acid	Generator
1,4-Dimethanesulphonoxybutane	Generator
Bisulphex	Generator
Busulphano	Generator
Busulphanum	Generator
Leucosulphan	Generator
Tetramethylene bis(methanesulfonic acid)	Generator
Tetramethylene bis(methanesulphonate)	Generator
Tetramethylene bis(methanesulphonic acid)	Generator
Busulphan	Generator
Busulphane	HMDB
Butanedioldimethanesulfonate	HMDB
Buzulfan	HMDB
Sulfabutin	HMDB
Sulphabutin	HMDB
Tetramethylene dimethane sulfonate	HMDB
Tetramethylenester kyseliny methansulfonove	HMDB
Busulfan wellcome brand	HMDB
Busulfex	HMDB
Orphan brand OF busulfan	HMDB
Busulfan glaxosmithkline brand	HMDB
Busulfan orphan brand	HMDB
Busulfan wellcome	HMDB
Myelosan	HMDB
Mylecytan	HMDB
Wellcome, busulfan	HMDB
Glaxo wellcome brand OF busulfan	HMDB
Glyzophrol	HMDB
Myléran	HMDB
Wellcome brand OF busulfan	HMDB
GlaxoSmithKline brand OF busulfan	HMDB
N-Butane-1,3-di(methylsulfonate)	HMDB

Chemical Formula

C₆H₁₄O₆S₂

Average Molecular Mass

246.302 g/mol

Monoisotopic Mass

246.023 g/mol

CAS Registry Number

55-98-1

IUPAC Name

4-(methanesulfonyloxy)butyl methanesulfonate

Traditional Name

busulfan

SMILES

CS(=O)(=O)OCCCCOS(C)(=O)=O

InChI Identifier

InChI=1S/C6H14O6S2/c1-13(7,8)11-5-3-4-6-12-14(2,9)10/h3-6H2,1-2H3

InChI Key

COVZYZSDYWQREU-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as organosulfonic acid esters. These are esters of sulfonic acid, which have the general structure RS(=O)2OR' (R,R' = organyl, not H).

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Organic sulfonic acids and derivatives

Sub Class

Organosulfonic acids and derivatives

Direct Parent

Organosulfonic acid esters

Alternative Parents

Substituents

Organosulfonic acid ester
Sulfonic acid ester
Sulfonyl
Methanesulfonate
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organosulfur compound
Organooxygen compound
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

methanesulfonate ester (CHEBI:28901 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

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	106-107°C
Boiling Point	Not Available
Solubility	6.9E+004 mg/L

Predicted Properties

Property	Value	Source
Water Solubility	5.16 g/L	ALOGPS
logP	-0.9	ALOGPS
logP	-0.76	ChemAxon
logS	-1.7	ALOGPS
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	86.74 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	49.57 m³·mol⁻¹	ChemAxon
Polarizability	23.64 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	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	splash10-0a6r-4910000000-e9ddf91161b812713ab4	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	splash10-014i-1490000000-7895468c598e6a0480c8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-014i-0390000000-19a6e15d2bf397b244b1	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-014i-0390000000-19a6e15d2bf397b244b1	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-014i-1490000000-7895468c598e6a0480c8	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0290000000-d4b566ed54a53c849786	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0udi-3910000000-3801100c88a8c43def33	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-004r-9500000000-3dec1d870a9203efd37f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-3090000000-aa607731139624cbe5bc	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-9110000000-7405cd0ebfa01ce907a0	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-004i-9000000000-4e28fa66f6cebb7272cc	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0uka-9530000000-c112640ccc30da208327	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a4j-9000000000-ed8101663b60977229ec	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-4f0ac4d1c58f92828a43	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-0090000000-1d2d39d4577a3e5e71ad	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-000j-2960000000-3752c572e539716a5e2e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-002f-9100000000-644c96579ffd326045dc	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

Completely absorbed from the gastrointestinal tract. Busulfan is a small, highly lipophilic molecule that crosses the blood-brain-barrier. The absolute bioavailability, if a single 2 mg IV bolus injection is given to adult patients, is 80% Њ± 20%. In children (1.5 - 6 years old), the absolute bioavailability was 68% Њ± 31%. When a single oral dose is given to patients, the area under the curve (AUC) was 130 ngдуўhr/mL. The peak plasma concentration when given orally is 30 ng/mL (after dose normalization to 2 mg). It takes 0.9 hours to reach peak plasma concentration after dose normalization to 4 mg.

Mechanism of Toxicity

Busulfan is an alkylating agent that contains 2 labile methanesulfonate groups attached to opposite ends of a 4-carbon alkyl chain. Once busulfan is hydrolyzed, the methanesulfonate groups are released and carbonium ions are produced. These carbonium ions alkylate DNA, which results in the interference of DNA replication and RNA transcription, ultimately leading to the disruption of nucleic acid function. Specifically, its mechanism of action through alkylation produces guanine-adenine intrastrand crosslinks. This occurs through an SN2 reaction in which the relatively nucleophilic guanine N7 attacks the carbon adjacent to the mesylate leaving group. This kind of damage cannot be repaired by cellular machinery and thus the cell undergoes apoptosis.

Metabolism

Busulfan is extensively metabolizes in the hepatic. Busulfan is predominantly metabolized by conjugation with glutathione, both spontaneously and by glutathione S-transferase (GST) catalysis. GSTA1 is the primary GST isoform that facilitates the the metabolism of busulfan. Other GST isoforms that are also involved are GSTM1 and GSTP1. At least 12 metabolites have been identified among which tetrahydrothiophene, tetrahydrothiophene 12-oxide, sulfolane, and 3-hydroxysulfolane were identified. These metabolites do not have cytotoxic activity. Route of Elimination: Following administration of 14C- labeled busulfan to humans, approximately 30% of the radioactivity was excreted into the urine over 48 hours; negligible amounts were recovered in feces. Less than 2% of the administered dose is excreted in the urine unchanged within 24 hours. Elimination of busulfan is independent of renal function. Half Life: 2.6 hours

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

1, carcinogenic to humans. (8)

Uses/Sources

For use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous (myeloid, myelocytic, granulocytic) leukemia (FDA has designated busulfan as an orphan drug for this use). It is also used as a component of pretransplant conditioning regimens in patients undergoing bone marrow transplantation for acute myeloid leukemia and nonmalignant diseases.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

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.

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

DB01008

HMDB ID

HMDB0015143

FooDB ID

Not Available

Phenol Explorer ID