Lomustine (T3D4700)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2014-09-11 02:05:33 UTC
Update Date2014-12-24 20:26:55 UTC
Accession NumberT3D4700
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.
Compound Type
  • Amine
  • Antineoplastic Agent, Alkylating
  • Drug
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
1-(2-Chloroethyl)-3-cyclohexylnitrosourea
Belustine
CCNU
Cecenu
CeeNU
Chloroethylcyclohexylnitrosourea
CINU
Cyclohexyl chloroethyl nitrosourea
Lomustina
Lomustinum
N-(2-Chloroethyl)-n'-cyclohexyl-N-nitrosourea
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
SMILESOC(=NC1CCCCC1)N(CCCl)N=O
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 KeyInChIKey=GQYIWUVLTXOXAJ-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
LogP2.83
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0059-8900000000-edefb2c60fb3a4723f1b2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-003r-9870000000-c1e5d9089d0ca3ebe9902016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004j-9600000000-553a8bea32ca95f8b8c92016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-9000000000-237df2753e3c796102702016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-05aj-4940000000-52228cb236f776094d552016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-9520000000-f52d4c064b87d135bcab2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-9100000000-c986da9a3b5f2025b30c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03e9-9410000000-3c91b816a1fd60d9fb412021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03e9-9100000000-e9795a3320548e7e05202021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9000000000-13ca0d883f27e08e4efe2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-3190000000-21d4dc32f394af73cd0d2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9000000000-99ed100e7c6291a96d1b2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9000000000-7fe5321df11e6429faf42021-10-11View Spectrum
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
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01206
HMDB IDHMDB15337
PubChem Compound ID3950
ChEMBL IDCHEMBL514
ChemSpider ID3813
KEGG IDC07079
UniProt IDNot Available
OMIM ID
ChEBI ID110898
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkLomustine
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

1. 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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
  3. Larkin JM, Hughes SA, Beirne DA, Patel PM, Gibbens IM, Bate SC, Thomas K, Eisen TG, Gore ME: A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma. Br J Cancer. 2007 Jan 15;96(1):44-8. Epub 2006 Dec 5. [17146474 ]
  4. Spiro T, Liu L, Gerson S: New cytotoxic agents for the treatment of metastatic malignant melanoma: temozolomide and related alkylating agents in combination with guanine analogues to abrogate drug resistance. Forum (Genova). 2000 Jul-Sep;10(3):274-85. [11007934 ]
Target Details
2. Stathmin-4
General Function:
Tubulin binding
Specific Function:
Exhibits microtubule-destabilizing activity.
Gene Name:
STMN4
Uniprot ID:
Q9H169
Molecular Weight:
22071.02 Da
References
  1. Liang XJ, Choi Y, Sackett DL, Park JK: Nitrosoureas inhibit the stathmin-mediated migration and invasion of malignant glioma cells. Cancer Res. 2008 Jul 1;68(13):5267-72. doi: 10.1158/0008-5472.CAN-07-6482. [18593927 ]
  2. Wu WW, Wang G, Liang XJ, Park JK, Shen RF: Covalent modification of stathmin by CCNU determined by FTMS analysis of modified proteins and tryptic peptides. Biochem Biophys Res Commun. 2008 Feb 29;367(1):7-13. Epub 2007 Dec 26. [18162179 ]