Identification

Name
Lomustine
Accession Number
DB01206
Description

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

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 233.695
Monoisotopic: 233.093104478
Chemical Formula
C9H16ClN3O2
Synonyms
  • 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
  • 1-(2-chloroethyl)-3-cyclohexylnitrosourea
  • Chloroethylcyclohexylnitrosourea
  • CINU
  • Cyclohexyl chloroethyl nitrosourea
  • Lomustina
  • Lomustine
  • Lomustinum
  • N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea
External IDs
  • NSC-79037

Pharmacology

Indication

For 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.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Lomustine 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 action

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.

TargetActionsOrganism
ADNA
cross-linking/alkylation
Humans
UStathmin-4
antagonist
Humans
Absorption

Well and rapidly absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding

50%

Metabolism

Hepatic. 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.

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Oral, 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Lomustine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Lomustine.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Lomustine.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Lomustine.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Lomustine.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Lomustine.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Lomustine.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Lomustine.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Lomustine.
AllopurinolThe risk or severity of adverse effects can be increased when Allopurinol is combined with Lomustine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

International/Other Brands
Belustine / CCNU / Cecenu
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CeenuCapsule, gelatin coated100 mg/1OralE.R. Squibb & Sons, L.L.C.2008-12-152014-06-30US flag
CeenuCapsule100 mgOralBristol Myers Squibb1976-12-312019-10-01Canada flag
CeenuCapsule, gelatin coated10 mg/1OralE.R. Squibb & Sons, L.L.C.2008-12-152016-04-15US flag
CeenuCapsule10 mgOralBristol Myers Squibb1976-12-31Not applicableCanada flag
CeenuCapsule, gelatin coated40 mg/1OralE.R. Squibb & Sons, L.L.C.2008-12-152016-04-15US flag
CeenuCapsule40 mgOralBristol Myers Squibb1976-12-31Not applicableCanada flag
GleostineCapsule, gelatin coated40 mg/1OralNextSource Biotechnology, LLC2014-08-18Not applicableUS flag
GleostineCapsule, gelatin coated100 mg/1OralNextSource Biotechnology, LLC2014-08-18Not applicableUS flag
GleostineCapsule, gelatin coated5 mg/1OralNextSource Biotechnology, LLC2015-11-052015-11-05US flag
GleostineCapsule, gelatin coated10 mg/1OralNextSource Biotechnology, LLC2014-08-18Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
CeenuLomustine (10 mg/1) + Lomustine (40 mg/1) + Lomustine (100 mg/1)KitOralBristol-Myers Squibb2009-05-212009-05-21US flag
CeenuLomustine (10 mg/1) + Lomustine (40 mg/1) + Lomustine (100 mg/1)KitOralBristol-Myers Squibb2009-05-212009-05-21US flag
CeenuLomustine (10 mg/1) + Lomustine (40 mg/1) + Lomustine (100 mg/1)KitOralBristol-Myers Squibb2009-05-212009-05-21US flag

Categories

ATC Codes
L01AD02 — Lomustine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as nitrosoureas. These 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.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic carbonic acids and derivatives
Sub Class
Ureas
Direct Parent
Nitrosoureas
Alternative Parents
Semicarbazides / Nitrosamides / Organopnictogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds / Alkyl chlorides
Substituents
Aliphatic homomonocyclic compound / Alkyl chloride / Alkyl halide / Carbonyl group / Hydrocarbon derivative / Nitrosamide / Nitrosourea / Organic n-nitroso compound / Organic nitrogen compound / Organic nitroso compound
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
organochlorine compound, N-nitrosoureas (CHEBI:6520)

Chemical Identifiers

UNII
7BRF0Z81KG
CAS number
13010-47-4
InChI Key
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

References

General References
Not Available
Human Metabolome Database
HMDB0015337
KEGG Drug
D00363
KEGG Compound
C07079
PubChem Compound
3950
PubChem Substance
46506562
ChemSpider
3813
BindingDB
50247919
RxNav
6466
ChEBI
6520
ChEMBL
CHEMBL514
ZINC
ZINC000003831006
Therapeutic Targets Database
DAP000991
PharmGKB
PA164749407
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lomustine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
MSDS
Download (56.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentCognition Disorders / Disability Evaluation / Glioblastoma Multiforme (GBM)1
3Active Not RecruitingTreatmentNeoplasms, Brain / Tumors of the Central Nervous System / Untreated Childhood Medulloblastoma1
3CompletedTreatmentAcute Myeloid Leukemia (AML)2
3CompletedTreatmentBrain and Central Nervous System Tumors4
3CompletedTreatmentGlioblastomas3
3CompletedTreatmentNeoplasms, Brain / Tumors of the Central Nervous System2
3CompletedTreatmentRecurrent Glioblastoma1
3RecruitingTreatmentAnaplastic Astrocytoma (AA) / Recurrent Anaplastic Astrocytoma1
3RecruitingTreatmentBrain and Central Nervous System Tumors1
3TerminatedTreatmentAnaplastic Astrocytoma (AA) / Glioblastomas1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bristol-Myers Squibb Co.
  • Group Health Cooperative
  • Mead Johnson and Co.
Dosage Forms
FormRouteStrength
CapsuleOral10 mg
CapsuleOral100 mg
CapsuleOral40 mg
Capsule, gelatin coatedOral10 mg/1
Capsule, gelatin coatedOral100 mg/1
Capsule, gelatin coatedOral40 mg/1
KitOral
Capsule, gelatin coatedOral5 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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)88-90 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Cross-linking/alkylation
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Tubulin binding
Specific Function
Exhibits microtubule-destabilizing activity.
Gene Name
STMN4
Uniprot ID
Q9H169
Uniprot Name
Stathmin-4
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
Humans
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou-Pan XR, Seree E, Zhou XJ, Placidi M, Maurel P, Barra Y, Rahmani R: Involvement of human liver cytochrome P450 3A in vinblastine metabolism: drug interactions. Cancer Res. 1993 Nov 1;53(21):5121-6. [PubMed:8221648]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Le Guellec C, Lacarelle B, Catalin J, Durand A: Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5. [PubMed:8258200]
  2. Lomustine Drug Monograph - BC Cancer [Link]

Drug created on June 13, 2005 07:24 / Updated on September 22, 2020 02:10

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