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Identification
NameLomustine
Accession NumberDB01206  (APRD00292)
TypeSmall Molecule
GroupsApproved
Description

An alkylating agent of value against both hematologic malignancies and solid tumors. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosoureaNot AvailableNot Available
1-(2-Chloroethyl)-3-cyclohexylnitrosoureaNot AvailableNot Available
BelustineNot AvailableNot Available
CCNUNot AvailableNot Available
CecenuNot AvailableNot Available
CeeNUNot AvailableNot Available
ChloroethylcyclohexylnitrosoureaNot AvailableNot Available
CINUNot AvailableNot Available
Cyclohexyl chloroethyl nitrosoureaNot AvailableNot Available
LomustinaSpanishINN
LomustinumLatinINN
N-(2-Chloroethyl)-n'-cyclohexyl-N-nitrosoureaNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ceenucapsule, gelatin coated10 mgoralE.R. Squibb & Sons, L.L.C.2008-12-152016-04-15Us
Ceenucapsule, gelatin coated40 mgoralE.R. Squibb & Sons, L.L.C.2008-12-152016-04-15Us
Lomustinecapsule, gelatin coated10 mgoralNext Source Biotechnology, Llc2014-07-29Not AvailableUs
Lomustinecapsule, gelatin coated40 mgoralNext Source Biotechnology, Llc2014-07-29Not AvailableUs
Lomustinecapsule, gelatin coated100 mgoralNext Source Biotechnology, Llc2014-07-29Not AvailableUs
Gleostinecapsule, gelatin coated10 mgoralNext Source Biotechnology, Llc2014-08-18Not AvailableUs
Gleostinecapsule, gelatin coated40 mgoralNext Source Biotechnology, Llc2014-08-18Not AvailableUs
Gleostinecapsule, gelatin coated100 mgoralNext Source Biotechnology, Llc2014-08-18Not AvailableUs
Ceenucapsule100 mgoralBristol Myers Squibb CanadaNot AvailableNot AvailableCanada
Ceenucapsule40 mgoralBristol Myers Squibb CanadaNot AvailableNot AvailableCanada
Ceenucapsule10 mgoralBristol Myers Squibb CanadaNot AvailableNot AvailableCanada
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
BelustineNot Available
CecenuNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number13010-47-4
WeightAverage: 233.695
Monoisotopic: 233.093104478
Chemical FormulaC9H16ClN3O2
InChI KeyGQYIWUVLTXOXAJ-UHFFFAOYSA-N
InChI
InChI=1S/C9H16ClN3O2/c10-6-7-13(12-15)9(14)11-8-4-2-1-3-5-8/h8H,1-7H2,(H,11,14)
IUPAC Name
3-(2-chloroethyl)-1-cyclohexyl-3-nitrosourea
SMILES
ClCCN(N=O)C(=O)NC1CCCCC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cyclohexylamines. These are organic compounds containing a cyclohexylamine moiety, which consist of a cyclohexane ring attached to an amine group.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassCyclohexylamines
Sub ClassNot Available
Direct ParentCyclohexylamines
Alternative Parents
Substituents
  • Cyclohexylamine
  • Nitrosourea
  • Nitrosamide
  • Semicarbazide
  • Organic nitrosamine
  • N-nitroso compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Alkyl halide
  • Alkyl chloride
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsLomustine is an alkylating agent of the nitrosourea type. Lomustine and its metabolites interferes with the function of DNA and RNA. It is cell cycle–phase nonspecific. Cancers form when some cells within the body multiply uncontrollably and abnormally. These cells then spread and destroy nearby tissues. Lomustine acts by slowing this process down. It kills cancer cells by damaging the DNA (the genetic material inside the cells) and stops them from dividing.
Mechanism of actionLomustine 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.
AbsorptionWell and rapidly absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein binding50%
Metabolism

Hepatic. Rapid and complete, with active metabolites.

Route of eliminationFollowing 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 lifeApproximately 94 minutes, however the metabolites have a serum half-life of 16 to 48 hours.
ClearanceNot Available
ToxicityOral, 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.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9962
Blood Brain Barrier+0.9383
Caco-2 permeable-0.5443
P-glycoprotein substrateNon-substrate0.6803
P-glycoprotein inhibitor INon-inhibitor0.837
P-glycoprotein inhibitor IINon-inhibitor0.8642
Renal organic cation transporterNon-inhibitor0.7664
CYP450 2C9 substrateNon-substrate0.763
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.651
CYP450 1A2 substrateNon-inhibitor0.8127
CYP450 2C9 substrateNon-inhibitor0.829
CYP450 2D6 substrateNon-inhibitor0.9159
CYP450 2C19 substrateNon-inhibitor0.7446
CYP450 3A4 substrateNon-inhibitor0.8499
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.789
Ames testAMES toxic0.9309
CarcinogenicityCarcinogens 0.5074
BiodegradationNot ready biodegradable0.7517
Rat acute toxicity3.5549 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8183
hERG inhibition (predictor II)Non-inhibitor0.8735
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral10 mg
Capsuleoral100 mg
Capsuleoral40 mg
Capsule, gelatin coatedoral10 mg
Capsule, gelatin coatedoral100 mg
Capsule, gelatin coatedoral40 mg
Prices
Unit descriptionCostUnit
Ceenu 100 mg capsule60.61USD capsule
Ceenu 40 mg capsule31.88USD capsule
CeeNU 300 mg capsule31.69USD capsule
Ceenu dose pack30.47USD each
Ceenu 10 mg capsule10.77USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point88-90 °CPhysProp
water solubility111 mg/LNot Available
logP2.83HANSCH,C & LEO,AJ (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.755 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity58.65 m3·mol-1ChemAxon
Polarizability23.61 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesL01AD02
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (56.6 KB)
Interactions
Drug Interactions
Drug
AtomoxetineThe CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
BendamustineIncreases toxicity through pharmacodynamic synergism. Additive myelosuppression.
TerbinafineTerbinafine may reduce the metabolism and clearance of Lomustine. Consider alternate therapy or monitor for therapeutic/adverse effects of Lomustine if Terbinafine is initiated, discontinued or dose changed.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food InteractionsNot Available

Targets

1. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: cross-linking/alkylation

Components

Name UniProt ID Details

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

2. Stathmin-4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Stathmin-4 Q9H169 Details

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. Pubmed
  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. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 11, 2014 14:34