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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
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
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ceenucapsule, gelatin coated10 mg/1oralE.R. Squibb & Sons, L.L.C.2008-12-152016-04-15Us
Ceenucapsule10 mgoralBristol Myers Squibb Canada1976-12-31Not applicableCanada
Ceenucapsule40 mgoralBristol Myers Squibb Canada1976-12-31Not applicableCanada
Ceenucapsule100 mgoralBristol Myers Squibb Canada1976-12-31Not applicableCanada
Ceenucapsule, gelatin coated40 mg/1oralE.R. Squibb & Sons, L.L.C.2008-12-152016-04-15Us
Gleostinecapsule, gelatin coated40 mg/1oralNext Source Biotechnology, Llc2014-08-18Not applicableUs
Gleostinecapsule, gelatin coated10 mg/1oralNext Source Biotechnology, Llc2014-08-18Not applicableUs
Gleostinecapsule, gelatin coated5 mg/1oralNext Source Biotechnology, Llc2015-11-05Not applicableUs
Gleostinecapsule, gelatin coated100 mg/1oralNext Source Biotechnology, Llc2014-08-18Not applicableUs
Lomustinecapsule, gelatin coated100 mg/1oralNext Source Biotechnology, Llc2014-07-292016-01-16Us
Lomustinecapsule, gelatin coated40 mg/1oralNext Source Biotechnology, Llc2014-07-292016-01-16Us
Lomustinecapsule, gelatin coated10 mg/1oralNext Source Biotechnology, Llc2014-07-292016-01-16Us
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BelustineNot Available
CecenuNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII7BRF0Z81KG
CAS number13010-47-4
WeightAverage: 233.695
Monoisotopic: 233.093104478
Chemical FormulaC9H16ClN3O2
InChI KeyInChIKey=GQYIWUVLTXOXAJ-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.
Related Articles
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 inhibitorNon-inhibitor0.829
CYP450 2D6 inhibitorNon-inhibitor0.9159
CYP450 2C19 inhibitorNon-inhibitor0.7446
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral10 mg
Capsuleoral100 mg
Capsuleoral40 mg
Capsule, gelatin coatedoral10 mg/1
Capsule, gelatin coatedoral40 mg/1
Capsule, gelatin coatedoral5 mg/1
Capsule, gelatin coatedoral100 mg/1
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 ReferencesNot Available
External Links
ATC CodesL01AD02
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (56.6 KB)
Interactions
Drug Interactions
Drug
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Lomustine.
ClozapineThe risk or severity of adverse effects can be increased when Lomustine is combined with Clozapine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Lomustine.
LeflunomideThe risk or severity of adverse effects can be increased when Lomustine is combined with Leflunomide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Lomustine.
NatalizumabThe risk or severity of adverse effects can be increased when Lomustine is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Lomustine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Lomustine.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Lomustine.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Lomustine.
TofacitinibLomustine may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Lomustine.
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
cross-linking/alkylation
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:11007934 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
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. [PubMed: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. [PubMed:18162179 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on April 11, 2014 14:34