Identification
- Summary
Lomustine is an alkylating agent used as a part of chemotherapeutic regimens for the treatment of primary and metastatic brain tumors as well as refractory or relapsed Hodgkin's disease in addition to surgical and/or radiotherapeutic treatments.
- Brand Names
- Ceenu, Gleostine
- Generic Name
- Lomustine
- DrugBank Accession Number
- DB01206
- Background
An alkylating agent of value against both hematologic malignancies and solid tumors.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Lomustine (DB01206)
- 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Metastatic brain tumor •••••••••••• Treatment of Primary brain tumor •••••••••••• Used in combination to treat Refractory hodgkin's disease •••••••••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism ADNA cross-linking/alkylationHumans UStathmin-4 antagonistHumans - 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
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Lomustine is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Lomustine. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Lomustine. Acetylsalicylic acid The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Lomustine. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Lomustine. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Belustine / CCNU / Cecenu
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ceenu Capsule 100 mg Oral Bristol Myers Squibb 1976-12-31 2019-10-01 Canada 
Ceenu Capsule, gelatin coated 40 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2008-12-15 2016-04-15 US 
Ceenu Capsule 10 mg Oral Bristol Myers Squibb 1976-12-31 Not applicable Canada Ceenu Capsule 40 mg Oral Bristol Myers Squibb 1976-12-31 Not applicable Canada Ceenu Capsule, gelatin coated 100 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2008-12-15 2014-06-30 US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Ceenu Lomustine (10 mg/1) + Lomustine (40 mg/1) + Lomustine (100 mg/1) Kit Oral Bristol-Myers Squibb 2009-05-21 2009-05-21 US Ceenu Lomustine (10 mg/1) + Lomustine (40 mg/1) + Lomustine (100 mg/1) Kit Oral Bristol-Myers Squibb 2009-05-21 2009-05-21 US Ceenu Lomustine (10 mg/1) + Lomustine (40 mg/1) + Lomustine (100 mg/1) Kit Oral Bristol-Myers Squibb 2009-05-21 2009-05-21 US
Categories
- ATC Codes
- L01AD02 — Lomustine
- Drug Categories
- Alkylating Activity
- Alkylating Drugs
- Amides
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Immunosuppressive Agents
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Nitroso Compounds
- Nitrosourea Compounds
- Nitrosoureas
- Noxae
- Toxic Actions
- 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)
- Affected organisms
- Humans and other mammals
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
- FDA Approved Drug Products: GLEOSTINE (lomustine) capsules [Link]
- External Links
- Human Metabolome Database
- HMDB0015337
- KEGG Drug
- D00363
- KEGG Compound
- C07079
- PubChem Compound
- 3950
- PubChem Substance
- 46506562
- ChemSpider
- 3813
- BindingDB
- 50247919
- 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
- MSDS
- Download (56.6 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Anaplastic Astrocytoma (AA) / Recurrent Anaplastic Astrocytoma 1 3 Active Not Recruiting Treatment Medulloblastomas 1 3 Active Not Recruiting Treatment Untreated Childhood Medulloblastoma 1 3 Completed Treatment Acute Myeloid Leukemia 2 3 Completed Treatment Brain and Central Nervous System Tumors 4
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Bristol-Myers Squibb Co.
- Group Health Cooperative
- Mead Johnson and Co.
- Dosage Forms
Form Route Strength Capsule Oral Capsule Oral 10 mg Capsule Oral 100 mg Capsule Oral 40 mg Capsule, gelatin coated Oral 10 mg/1 Capsule, gelatin coated Oral 100 mg/1 Capsule, gelatin coated Oral 40 mg/1 Kit Oral Capsule, liquid filled Oral 40 mg Capsule, liquid filled Oral 100 mg Capsule, gelatin coated Oral 5 mg/1 - Prices
Unit description Cost Unit Ceenu 100 mg capsule 60.61USD capsule Ceenu 40 mg capsule 31.88USD capsule CeeNU 300 mg capsule 31.69USD capsule Ceenu dose pack 30.47USD each Ceenu 10 mg capsule 10.77USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 88-90 °C PhysProp water solubility 111 mg/L Not Available logP 2.83 HANSCH,C & LEO,AJ (1985) - Predicted Properties
Property Value Source Water Solubility 0.755 mg/mL ALOGPS logP 2.62 ALOGPS logP 2.16 Chemaxon logS -2.5 ALOGPS pKa (Strongest Acidic) 14.05 Chemaxon pKa (Strongest Basic) -5.3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 61.77 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 58.65 m3·mol-1 Chemaxon Polarizability 23.61 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9962 Blood Brain Barrier + 0.9383 Caco-2 permeable - 0.5443 P-glycoprotein substrate Non-substrate 0.6803 P-glycoprotein inhibitor I Non-inhibitor 0.837 P-glycoprotein inhibitor II Non-inhibitor 0.8642 Renal organic cation transporter Non-inhibitor 0.7664 CYP450 2C9 substrate Non-substrate 0.763 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.651 CYP450 1A2 substrate Non-inhibitor 0.8127 CYP450 2C9 inhibitor Non-inhibitor 0.829 CYP450 2D6 inhibitor Non-inhibitor 0.9159 CYP450 2C19 inhibitor Non-inhibitor 0.7446 CYP450 3A4 inhibitor Non-inhibitor 0.8499 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.789 Ames test AMES toxic 0.9309 Carcinogenicity Carcinogens 0.5074 Biodegradation Not ready biodegradable 0.7517 Rat acute toxicity 3.5549 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.8183 hERG inhibition (predictor II) Non-inhibitor 0.8735
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0059-8900000000-edefb2c60fb3a4723f1b Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-9200000000-d12e978220186b4ce00e Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9020000000-3b7974d386b4d0cfffdc Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-9000000000-b3b48b60bc27c2d528ee Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9000000000-8b00f60898b71e96d74e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9000000000-1e7ab0de34d70ac0a917 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-01q0-9000000000-035183ece3ea18896e77 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 151.4865963 predictedDarkChem Lite v0.1.0 [M-H]- 154.48265 predictedDeepCCS 1.0 (2019) [M+H]+ 152.4145963 predictedDarkChem Lite v0.1.0 [M+H]+ 156.86876 predictedDeepCCS 1.0 (2019) [M+Na]+ 151.7866963 predictedDarkChem Lite v0.1.0 [M+Na]+ 164.51122 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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Yes
Cross-linking/alkylation
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
Enzymes
- 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
- 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
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54