Lomustine (CHEM003658)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (2)XML
Record Information
Version1.0
Creation Date2014-09-11 02:05:33 UTC
Update Date2016-11-09 01:09:11 UTC
Accession NumberCHEM003658
Identification
Common NameLomustine
ClassSmall Molecule
DescriptionLomustine is only found in individuals that have used or taken this drug. It is an alkylating agent of value against both hematologic malignancies and solid tumors. Lomustine is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA (at the O6 position of guanine-containing bases) and RNA, thus inducing cytotoxicity. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Nitrosureas generally lack cross-resistance with other alkylating agents. As lomustine is a nitrosurea, it may also inhibit several key processes such as carbamoylation and modification of cellular proteins.
Contaminant Sources
  • HMDB Contaminants - Urine
  • IARC Carcinogens Group 2A
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amine
  • Antineoplastic Agent, Alkylating
  • Drug
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosoureaChEBI
1-(2-Chloroethyl)-3-cyclohexylnitrosoureaChEBI
BelustineChEBI
CCNUChEBI
CecenuChEBI
CeeNUChEBI
ChloroethylcyclohexylnitrosoureaChEBI
CINUChEBI
Cyclohexyl chloroethyl nitrosoureaChEBI
LomustinaChEBI
LomustinumChEBI
N-(2-Chloroethyl)-n'-cyclohexyl-N-nitrosoureaChEBI
GleostineKegg
Bristol-myers squibb brand OF lomustineHMDB
Rhône-poulenc rorer brand OF lomustineHMDB
Medac brand OF lomustineHMDB
Bristol myers squibb brand OF lomustineHMDB
Rhône poulenc rorer brand OF lomustineHMDB
Lomustine medac brandHMDB
Chemical FormulaC9H16ClN3O2
Average Molecular Mass233.695 g/mol
Monoisotopic Mass233.093 g/mol
CAS Registry Number13010-47-4
IUPAC Name3-(2-chloroethyl)-1-cyclohexyl-3-nitrosourea
Traditional Namelomustine
SMILESClCCN(N=O)C(=O)NC1CCCCC1
InChI IdentifierInChI=1S/C9H16ClN3O2/c10-6-7-13(12-15)9(14)11-8-4-2-1-3-5-8/h8H,1-7H2,(H,11,14)
InChI KeyGQYIWUVLTXOXAJ-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 homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • 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 Point88 - 90°C
Boiling PointNot Available
Solubility111 mg/L
Predicted Properties
PropertyValueSource
Water Solubility0.76 g/LALOGPS
logP2.62ALOGPS
logP2.16ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)13.3ChemAxon
pKa (Strongest Basic)-5.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area61.77 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity58.65 m³·mol⁻¹ChemAxon
Polarizability23.61 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0059-8900000000-edefb2c60fb3a4723f1bSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-003r-9870000000-c1e5d9089d0ca3ebe990Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004j-9600000000-553a8bea32ca95f8b8c9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-9000000000-237df2753e3c79610270Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-05aj-4940000000-52228cb236f776094d55Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-9520000000-f52d4c064b87d135bcabSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-9100000000-c986da9a3b5f2025b30cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03e9-9410000000-3c91b816a1fd60d9fb41Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03e9-9100000000-e9795a3320548e7e0520Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9000000000-13ca0d883f27e08e4efeSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-3190000000-21d4dc32f394af73cd0dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9000000000-99ed100e7c6291a96d1bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9000000000-7fe5321df11e6429faf4Spectrum
Toxicity Profile
Route of ExposureWell and rapidly absorbed from the gastrointestinal tract.
Mechanism of ToxicityLomustine is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA (at the O6 position of guanine-containing bases) and RNA, thus inducing cytotoxicity. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Nitrosureas generally lack cross-resistance with other alkylating agents. As lomustine is a nitrosurea, it may also inhibit several key processes such as carbamoylation and modification of cellular proteins.
MetabolismHepatic. Rapid and complete, with active metabolites. Route of Elimination: Following oral administration of radioactive CeeNU at doses ranging from 30 mg/m2 to 100 mg/m2, about half of the radioactivity given was excreted in the urine in the form of degradation products within 24 hours. Half Life: Approximately 94 minutes, however the metabolites have a serum half-life of 16 to 48 hours.
Toxicity ValuesOral, rat: LD50 = 70 mg/kg. Pulmonary toxicity has been reported at cumulative doses usually greater than 1,100 mg/m2. There is one report of pulmonary toxicity at a cumulative dose of only 600 mg. The onset of toxicity has varied from 6 months after initiation of therapy, to as late as 15 years after.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2A, probably carcinogenic to humans. (1)
Uses/SourcesFor the treatment of primary and metastatic brain tumors as a component of combination chemotherapy in addition to appropriate surgical and/or radiotherapeutic procedures. Also used in combination with other agents as secondary therapy for the treatment of refractory or relapsed Hodgkin's disease.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB01206
HMDB IDHMDB0015337
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkLomustine
Chemspider ID3813
ChEBI ID6520
PubChem Compound ID3950
Kegg Compound IDC07079
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSLink
General References
1. https://www.ncbi.nlm.nih.gov/pubmed/?term=12153595
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=19901016
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=20719460
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=22577051
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=24293673
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=24368412
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=24516018
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=6762924