Identification
- Summary
Carmustine is an alkylating agent used in the treatment of various malignancies, including brain tumours and multiple myeloma, among others.
- Brand Names
- Bicnu, Gliadel
- Generic Name
- Carmustine
- DrugBank Accession Number
- DB00262
- Background
A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Carmustine (DB00262)
- Weight
- Average: 214.05
Monoisotopic: 213.007181961 - Chemical Formula
- C5H9Cl2N3O2
- Synonyms
- BCNU
- bis-chloroethylnitrosourea
- Bischloroethyl nitrosourea
- Carmustina
- Carmustine
- Carmustinum
- N,N'-Bis(2-chloroethyl)-N-nitrosourea
- External IDs
- DTI-015
- FDA-0345
- NSC-409962
- SK 27702
- SK-27702
- SRI 1720
- SRI-1720
Pharmacology
- Indication
For the treatment of brain tumors, multiple myeloma, Hodgkin's disease and Non-Hodgkin's lymphomas.
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 Symptomatic treatment of Astrocytoma •••••••••••• ••••••••• Symptomatic treatment of Brainstem glioma •••••••••••• ••••••••• Symptomatic treatment of Ependymoma •••••••••••• ••••••••• Symptomatic treatment of Glioblastoma •••••••••••• ••••••••• Symptomatic treatment of Medulloblastoma •••••••••••• ••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Carmustine is one of the nitrosoureas indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in treatment of brain tumors, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphomas. Although it is generally agreed that carmustine alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.
- Mechanism of action
Carmustine causes cross-links in DNA and RNA, leading to the inhibition of DNA synthesis, RNA production and RNA translation (protein synthesis). Carmustine also binds to and modifies (carbamoylates) glutathione reductase. This leads to cell death.
Target Actions Organism ARNA other/unknownHumans AGlutathione reductase, mitochondrial inhibitorHumans ADNA other/unknownHumans - Absorption
5 to 28% bioavailability
- Volume of distribution
Not Available
- Protein binding
80%
- Metabolism
Hepatic and rapid with active metabolites. Metabolites may persist in the plasma for several days.
- Route of elimination
Approximately 60% to 70% of a total dose is excreted in the urine in 96 hours and about 10% as respiratory CO2.
- Half-life
15-30 minutes
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The oral LD50s in rat and mouse are 20 mg/kg and 45 mg/kg, respectively. Side effects include leukopenia, thrombocytopenia, nausea. Toxic effects include pulmonary fibrosis (20-0%) and bone marrow toxicity.
- 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 softwareAbacavir Carmustine may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Carmustine can be increased when it is combined with Abametapir. Abatacept The metabolism of Carmustine can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Carmustine. Abiraterone The serum concentration of Carmustine can be increased when it is combined with Abiraterone. - Food Interactions
- Avoid echinacea.
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
- Becenun / Carmubris / Carustine (Curacell Biotech) / Nitrumon
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bicnu Kit 100 mg/30mL Intravenous E.R. Squibb & Sons, L.L.C. 2009-06-01 2015-09-30 US 
BiCNU Injection, powder, lyophilized, for solution; Kit 100 mg/30mL Intravenous Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc. 2013-04-04 Not applicable US BiCNU Powder, for solution 100 mg / vial Intravenous Marcan Pharmaceuticals Inc 1975-12-31 Not applicable Canada 
Carmustine Injection, powder, lyophilized, for solution; Kit 300 mg/100mL Intravenous Accord Healthcare Inc. 2022-08-18 Not applicable US Carmustine Injection, powder, lyophilized, for solution; Kit 50 mg/20mL Intravenous Accord Healthcare Inc. 2022-08-18 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Carmustine Injection, powder, lyophilized, for solution; Kit 100 mg/30mL Intravenous Alembic Pharmaceuticals Inc. 2023-10-20 Not applicable US Carmustine Kit 100 mg/30mL Intravenous Dr. Reddy's Laboratories Inc. 2021-10-04 Not applicable US Carmustine Injection, powder, lyophilized, for solution; Kit 100 mg/30mL Intravenous Amneal Pharmaceuticals LLC 2018-10-22 Not applicable US Carmustine Injection, powder, lyophilized, for solution; Kit 100 mg/30mL Intravenous Navinta Llc 2020-12-29 Not applicable US Carmustine Injection, powder, lyophilized, for solution; Kit 100 mg/30mL Intravenous Novadoz Pharmaceuticals Llc 2023-05-11 Not applicable US
Categories
- ATC Codes
- L01AD01 — Carmustine
- Drug Categories
- Alkylating Activity
- Alkylating Drugs
- Amides
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Antineoplastic and Immunomodulating Agents
- Cardiotoxic antineoplastic agents
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- 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 acyclic compound / Alkyl chloride / Alkyl halide / Carbonyl group / Hydrocarbon derivative / Nitrosamide / Nitrosourea / Organic n-nitroso compound / Organic nitrogen compound / Organic nitroso compound
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- organochlorine compound, N-nitrosoureas (CHEBI:3423)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- U68WG3173Y
- CAS number
- 154-93-8
- InChI Key
- DLGOEMSEDOSKAD-UHFFFAOYSA-N
- InChI
- InChI=1S/C5H9Cl2N3O2/c6-1-3-8-5(11)10(9-12)4-2-7/h1-4H2,(H,8,11)
- IUPAC Name
- 1,3-bis(2-chloroethyl)-1-nitrosourea
- SMILES
- ClCCNC(=O)N(CCCl)N=O
References
- General References
- FDA Approved Drug Products: BiCNU (carmustine) for intravenous injection [Link]
- External Links
- Human Metabolome Database
- HMDB0014407
- KEGG Drug
- D00254
- KEGG Compound
- C06873
- PubChem Compound
- 2578
- PubChem Substance
- 46506980
- ChemSpider
- 2480
- BindingDB
- 50015950
- 2105
- ChEBI
- 3423
- ChEMBL
- CHEMBL513
- ZINC
- ZINC000003830387
- Therapeutic Targets Database
- DAP000041
- PharmGKB
- PA448810
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Carmustine
- FDA label
- Download (4.55 MB)
- MSDS
- Download (195 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 Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type / Refractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type 1 3 Completed Treatment Astrocytoma / Glioblastoma Multiforme (GBM) / Glioma 1 3 Completed Treatment Brain and Central Nervous System Tumors 3 3 Completed Treatment Breast Cancer 1 3 Completed Treatment Diffuse Large B-Cell Lymphoma (DLBCL) 1
Pharmacoeconomics
- Manufacturers
- Eisai inc
- Bristol laboratories inc div bristol myers co
- Packagers
- Bristol-Myers Squibb Co.
- Eisai Inc.
- Mead Johnson and Co.
- MGI Pharma
- Dosage Forms
Form Route Strength Kit Intravenous 100 mg/30mL Powder Parenteral 100 MG Powder, for solution Intravenous 100 mg / vial Injection, solution 100 mg Powder Parenteral 102 mg/1vial Injection, powder, for solution Intravenous 100 mg Injection, powder, lyophilized, for solution Intravenous 100 mg Injection, powder, for solution Parenteral 100 mg Injection, solution, concentrate Intravenous 300 mg Injection, solution, concentrate Intravenous 50 mg Injection, solution, concentrate Intravenous 100 mg Powder Parenteral 300 MG Powder Parenteral 50 MG Powder, for solution Intravenous; Parenteral 100 MG For solution; kit Intravenous 100 mg/30mL Injection, powder, lyophilized, for solution; kit Intravenous 100 mg/30mL Injection, powder, lyophilized, for solution; kit Intravenous 300 mg/100mL Injection, powder, lyophilized, for solution; kit Intravenous 50 mg/20mL Wafer Intracavitary 7.7 mg/1 Implant Intralesional 7.7 mg Wafer Intralesional 7.7 mg Wafer 7.7 mg - Prices
Unit description Cost Unit Gliadel Wafer 8 7.7 mg Wafers Box 22611.26USD box Gliadel wafer 3667.95USD each Bicnu 100 mg vial 205.69USD vial 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) 31 °C PhysProp water solubility 4000 mg/L (at 25 °C) MERCK (1989) logP 1.53 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 1.53 mg/mL ALOGPS logP 1.24 ALOGPS logP 1.02 Chemaxon logS -2.2 ALOGPS pKa (Strongest Acidic) 13.36 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 5 Chemaxon Refractivity 46.98 m3·mol-1 Chemaxon Polarizability 18.8 Å3 Chemaxon Number of Rings 0 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 + 1.0 Blood Brain Barrier + 0.9533 Caco-2 permeable - 0.5621 P-glycoprotein substrate Non-substrate 0.7552 P-glycoprotein inhibitor I Non-inhibitor 0.797 P-glycoprotein inhibitor II Non-inhibitor 0.8778 Renal organic cation transporter Non-inhibitor 0.8177 CYP450 2C9 substrate Non-substrate 0.7656 CYP450 2D6 substrate Non-substrate 0.8491 CYP450 3A4 substrate Non-substrate 0.672 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.9031 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9131 Ames test AMES toxic 0.9577 Carcinogenicity Carcinogens 0.688 Biodegradation Not ready biodegradable 0.5596 Rat acute toxicity 3.9975 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.7278 hERG inhibition (predictor II) Non-inhibitor 0.919
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0bu0-6900000000-7ee333c26479b9275253 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-9760000000-12f518b3ab530ca90b41 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9210000000-bcad130b3d61d6d0c470 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-9200000000-55d2576124ee9bcc2c43 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9000000000-bcaf33058a9ce6260ecd Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-9000000000-dcab83cd228811fcf9cf Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9000000000-510a6f1f7d25d8fe4740 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]- 134.7377 predictedDarkChem Lite v0.1.0 [M-H]- 136.07433 predictedDeepCCS 1.0 (2019) [M+H]+ 135.8245 predictedDarkChem Lite v0.1.0 [M+H]+ 139.82985 predictedDeepCCS 1.0 (2019) [M+Na]+ 134.7269 predictedDarkChem Lite v0.1.0 [M+Na]+ 148.75613 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Yes
Other/unknown
References
- Lin SH, Kleinberg LR: Carmustine wafers: localized delivery of chemotherapeutic agents in CNS malignancies. Expert Rev Anticancer Ther. 2008 Mar;8(3):343-59. doi: 10.1586/14737140.8.3.343. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Nadp binding
- Specific Function
- Maintains high levels of reduced glutathione in the cytosol.
- Gene Name
- GSR
- Uniprot ID
- P00390
- Uniprot Name
- Glutathione reductase, mitochondrial
- Molecular Weight
- 56256.565 Da
References
- Akella SS, Harris C: Pyridine nucleotide flux and glutathione oxidation in the cultured rat conceptus. Reprod Toxicol. 1999 May-Jun;13(3):203-13. [Article]
- Kirsch JD, Yi AK, Spitz DR, Krieg AM: Accumulation of glutathione disulfide mediates NF-kappaB activation during immune stimulation with CpG DNA. Antisense Nucleic Acid Drug Dev. 2002 Oct;12(5):327-40. [Article]
- Vallyathan V, Mega JF, Shi X, Dalal NS: Enhanced generation of free radicals from phagocytes induced by mineral dusts. Am J Respir Cell Mol Biol. 1992 Apr;6(4):404-13. [Article]
- Brodie AE, Reed DJ: Glutathione disulfide reduction in tumor mitochondria after t-butyl hydroperoxide treatment. Chem Biol Interact. 1992 Sep 28;84(2):125-32. [Article]
- Jopperi-Davis KS, Park MS, Rogers LK, Backes CH Jr, Lim IK, Smith CV: Compartmental inhibition of hepatic glutathione reductase activities by 1,3-bis(2-chloroethyl)-N-nitrosourea (BCNU) in Sprague-Dawley and Fischer-344 rats. Toxicol Lett. 2004 Mar 7;147(3):219-28. [Article]
- Doroshenko N, Doroshenko P: The glutathione reductase inhibitor carmustine induces an influx of Ca2+ in PC12 cells. Eur J Pharmacol. 2004 Aug 16;497(1):17-24. [Article]
- Powell SR, Puglia CD: Effect of inhibition of glutathione reductase by carmustine on central nervous system oxygen toxicity. J Pharmacol Exp Ther. 1987 Jan;240(1):111-7. [Article]
- Puglia CD, Powell SR: Inhibition of cellular antioxidants: a possible mechanism of toxic cell injury. Environ Health Perspect. 1984 Aug;57:307-11. [Article]
Yes
Other/unknown
References
- 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]
- Johannessen TC, Bjerkvig R, Tysnes BB: DNA repair and cancer stem-like cells--potential partners in glioma drug resistance? Cancer Treat Rev. 2008 Oct;34(6):558-67. doi: 10.1016/j.ctrv.2008.03.125. Epub 2008 May 22. [Article]
- Lin SH, Kleinberg LR: Carmustine wafers: localized delivery of chemotherapeutic agents in CNS malignancies. Expert Rev Anticancer Ther. 2008 Mar;8(3):343-59. doi: 10.1586/14737140.8.3.343. [Article]
- Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, Pena-Diaz J, Otterlei M, Slupphaug G, Krokan HE: Alkylation damage in DNA and RNA--repair mechanisms and medical significance. DNA Repair (Amst). 2004 Nov 2;3(11):1389-407. [Article]
- Zhang Q, Ohannesian DW, Kreklau EL, Erickson LC: Modulation of 1,3-bis-(2-chloroethyl)-1-nitrosourea resistance in human tumor cells using hammerhead ribozymes designed to degrade O6-methylguanine DNA methyltransferase mRNA. J Pharmacol Exp Ther. 2001 Jul;298(1):141-7. [Article]
- He YH, Xu Y, Kobune M, Wu M, Kelley MR, Martin WJ 2nd: Escherichia coli FPG and human OGG1 reduce DNA damage and cytotoxicity by BCNU in human lung cells. Am J Physiol Lung Cell Mol Physiol. 2002 Jan;282(1):L50-5. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54