Tmic
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2014-09-11 02:04:43 UTC
Update Date2014-12-24 20:26:55 UTC
Accession NumberT3D4681
Identification
Common NameCarmustine
ClassSmall Molecule
DescriptionCarmustine is a cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985).
Compound Type
  • Amine
  • Antineoplastic Agent, Alkylating
  • Drug
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
BCNU
Becenun
Bicnu
BiCNU
bis-chloroethylnitrosourea
Bischlorethylnitrosourea
Bischlorethylnitrosurea
Bischloroethyl nitrosourea
Carmubris
Carmustin
Carmustina
Carmustinum
Carustine
Gliadel
Gliadel Wafer
N,N'-Bis(2-chloroethyl)-N-nitrosourea
Nitrumon
Chemical FormulaC5H9Cl2N3O2
Average Molecular Mass214.050 g/mol
Monoisotopic Mass213.007 g/mol
CAS Registry Number154-93-8
IUPAC Name1,3-bis(2-chloroethyl)-3-nitrosourea
Traditional Namecarmustine
SMILESOC(=NCCCl)N(CCCl)N=O
InChI IdentifierInChI=1S/C5H9Cl2N3O2/c6-1-3-8-5(11)10(9-12)4-2-7/h1-4H2,(H,8,11)
InChI KeyInChIKey=DLGOEMSEDOSKAD-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as nitrosoureas. Nitrosoureas are compounds containing a nitro group and an urea group N-N linked together, with the general structure R1N(R2)C(=O)N(R3)N=O.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassOrganic carbonic acids and derivatives
Sub ClassUreas
Direct ParentNitrosoureas
Alternative Parents
Substituents
  • Nitrosourea
  • Semicarbazide
  • Nitrosamide
  • Organic n-nitroso compound
  • Organic nitroso compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Alkyl chloride
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Organic nitrogen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point31°C
Boiling PointNot Available
Solubility4000 mg/L (at 25°C)
LogP1.53
Predicted Properties
PropertyValueSource
Water Solubility1.53 g/LALOGPS
logP1.24ALOGPS
logP1.02ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)11.96ChemAxon
pKa (Strongest Basic)-5.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area61.77 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity46.98 m³·mol⁻¹ChemAxon
Polarizability18.8 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0bu0-6900000000-7ee333c26479b9275253View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-06vi-9630000000-1b262631b4a720cd9ebaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a6r-9500000000-fbebb9877cfb22d2c3d8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03fr-9000000000-86de321ebee3984d7705View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-116u-4930000000-a2c48761c56e3640e06bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004l-6900000000-fc62a96dc02889b5a3b7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004l-9200000000-d116bdf5580083ca15c7View in MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityCarmustine causes cross-links in DNA and RNA, leading to the inhibition of DNA synthesis, RNA production and RNA translation (protein synthesis). Carmustine also binds to and modifies (carbamoylates) glutathione reductase. This leads to cell death.
MetabolismHepatic and rapid with active metabolites. Metabolites may persist in the plasma for several days. Route of Elimination: Approximately 60% to 70% of a total dose is excreted in the urine in 96 hours and about 10% as respiratory CO2. Half Life: 15-30 minutes
Toxicity ValuesThe oral LD50s in rat and mouse are 20 mg/kg and 45 mg/kg, respectively.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2A, probably carcinogenic to humans. (1)
Uses/SourcesFor the treatment of brain tumors, multiple myeloma, Hodgkin's disease and Non-Hodgkin's lymphomas.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00262
HMDB IDHMDB14407
PubChem Compound ID2578
ChEMBL IDCHEMBL513
ChemSpider ID2480
KEGG IDC06873
UniProt IDNot Available
OMIM ID
ChEBI ID3423
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkCarmustine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Nadp binding
Specific Function:
Maintains high levels of reduced glutathione in the cytosol.
Gene Name:
GSR
Uniprot ID:
P00390
Molecular Weight:
56256.565 Da
References
  1. Akella SS, Harris C: Pyridine nucleotide flux and glutathione oxidation in the cultured rat conceptus. Reprod Toxicol. 1999 May-Jun;13(3):203-13. [10378469 ]
  2. Kirsch JD, Yi AK, Spitz DR, Krieg AM: Accumulation of glutathione disulfide mediates NF-kappaB activation during immune stimulation with CpG DNA. Antisense Nucleic Acid Drug Dev. 2002 Oct;12(5):327-40. [12477282 ]
  3. Vallyathan V, Mega JF, Shi X, Dalal NS: Enhanced generation of free radicals from phagocytes induced by mineral dusts. Am J Respir Cell Mol Biol. 1992 Apr;6(4):404-13. [1312851 ]
  4. Brodie AE, Reed DJ: Glutathione disulfide reduction in tumor mitochondria after t-butyl hydroperoxide treatment. Chem Biol Interact. 1992 Sep 28;84(2):125-32. [1394620 ]
  5. Jopperi-Davis KS, Park MS, Rogers LK, Backes CH Jr, Lim IK, Smith CV: Compartmental inhibition of hepatic glutathione reductase activities by 1,3-bis(2-chloroethyl)-N-nitrosourea (BCNU) in Sprague-Dawley and Fischer-344 rats. Toxicol Lett. 2004 Mar 7;147(3):219-28. [15104113 ]
  6. Doroshenko N, Doroshenko P: The glutathione reductase inhibitor carmustine induces an influx of Ca2+ in PC12 cells. Eur J Pharmacol. 2004 Aug 16;497(1):17-24. [15321730 ]
  7. Powell SR, Puglia CD: Effect of inhibition of glutathione reductase by carmustine on central nervous system oxygen toxicity. J Pharmacol Exp Ther. 1987 Jan;240(1):111-7. [3806383 ]
  8. Puglia CD, Powell SR: Inhibition of cellular antioxidants: a possible mechanism of toxic cell injury. Environ Health Perspect. 1984 Aug;57:307-11. [6094175 ]
2. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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. [17016423 ]
  2. Johannessen TC, Bjerkvig R, Tysnes BB: DNA repair and cancer stem-like cells--potential partners in glioma drug resistance? Cancer Treat Rev. 2008 Oct;34(6):558-67. doi: 10.1016/j.ctrv.2008.03.125. Epub 2008 May 22. [18501520 ]
  3. Lin SH, Kleinberg LR: Carmustine wafers: localized delivery of chemotherapeutic agents in CNS malignancies. Expert Rev Anticancer Ther. 2008 Mar;8(3):343-59. doi: 10.1586/14737140.8.3.343. [18366283 ]
  4. Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, Pena-Diaz J, Otterlei M, Slupphaug G, Krokan HE: Alkylation damage in DNA and RNA--repair mechanisms and medical significance. DNA Repair (Amst). 2004 Nov 2;3(11):1389-407. [15380096 ]
  5. Zhang Q, Ohannesian DW, Kreklau EL, Erickson LC: Modulation of 1,3-bis-(2-chloroethyl)-1-nitrosourea resistance in human tumor cells using hammerhead ribozymes designed to degrade O6-methylguanine DNA methyltransferase mRNA. J Pharmacol Exp Ther. 2001 Jul;298(1):141-7. [11408535 ]
  6. He YH, Xu Y, Kobune M, Wu M, Kelley MR, Martin WJ 2nd: Escherichia coli FPG and human OGG1 reduce DNA damage and cytotoxicity by BCNU in human lung cells. Am J Physiol Lung Cell Mol Physiol. 2002 Jan;282(1):L50-5. [11741815 ]
3. RNA
References
  1. Lin SH, Kleinberg LR: Carmustine wafers: localized delivery of chemotherapeutic agents in CNS malignancies. Expert Rev Anticancer Ther. 2008 Mar;8(3):343-59. doi: 10.1586/14737140.8.3.343. [18366283 ]