{{cs1 config|name-list-style=vanc|display-authors=6}} {{chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 487305398 | ImageFile = Carmustine.svg | ImageClass = skin-invert-image | ImageFile_Ref = {{chemboximage|correct|??}} | ImageName = Skeletal formula of carmustine | ImageFile1 = Carmustine ball-and-stick.png | ImageClass1 = bg-transparent | ImageName1 = Ball-and-stick model of carmustine molecule | IUPACName = 1,3-Bis(2-chloroethyl)-1-nitrosourea<ref>{{PubChem|2578}}</ref> | OtherNames = ''N'',''N'''-Bis(2-chloroethyl)-''N''-nitrosourea, bis-chloroethylnitrosourea, BCNU |Section1={{Chembox Identifiers | CASNo = 154-93-8 | CASNo_Ref = {{cascite|correct|CAS}} | PubChem = 2578 | ChemSpiderID = 2480 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | UNII = U68WG3173Y | UNII_Ref = {{fdacite|correct|FDA}} | EINECS = 205-838-2 | UNNumber = 2811 | DrugBank = DB00262 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | KEGG = D00254 | KEGG_Ref = {{keggcite|correct|kegg}} | MeSHName = Carmustine | ChEBI = 3423 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEMBL = 513 | ChEMBL_Ref = {{ebicite|correct|EBI}} | RTECS = YS2625000 | SMILES = C(CCl)NC(=O)N(CCCl)N=O | StdInChI = 1S/C5H9Cl2N3O2/c6-1-3-8-5(11)10(9-12)4-2-7/h1-4H2,(H,8,11) | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = DLGOEMSEDOSKAD-UHFFFAOYSA-N | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} }} |Section2={{Chembox Properties | C=5 | H=9 | Cl=2 | N=3 | O=2 | Appearance = Orange crystals | Odor = Odourless | MeltingPtC = 30 | LogP = 1.375 | pKa = 10.194 | pKb = 3.803 }} |Section6={{Chembox Pharmacology | ATCCode_prefix = L01 | ATCCode_suffix = AD01 | ATC_Supplemental = | ATCvet = | Licence_EU = yes | INN = | INN_EMA = | Licence_US = | Legal_status = | Legal_AU = S4 | Legal_AU_comment = | Legal_CA = | Legal_CA_comment = | Legal_NZ = | Legal_NZ_comment = | Legal_UK = POM | Legal_UK_comment = <ref>{{cite web | title=Carmustine 100mg Powder and solvent for Solution for Infusion - Summary of Product Characteristics (SmPC) | website=(emc) | date=24 March 2020 | url=https://www.medicines.org.uk/emc/product/11176/smpc }}</ref><ref>{{cite web | title=Gliadel 7.7mg Implant - Summary of Product Characteristics (SmPC) | website=(emc) | date=15 June 2020 | url=https://www.medicines.org.uk/emc/product/36/smpc }}</ref> | Legal_US = Rx-only | Legal_US_comment = <ref>{{cite web | title=Bicnu- carmustine kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6cbb63c-e0b1-43ee-ad6f-408da0772079 | access-date=27 February 2021}}</ref><ref>{{cite web | title=Gliadel- carmustine wafer | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=38962a55-a514-4c48-bea5-f99a8da4beec | access-date=27 February 2021}}</ref> | Legal_EU = Rx-only | Legal_EU_comment = | Legal_UN = | Legal_UN_comment = | Pregnancy_category = | Pregnancy_AU = D | Pregnancy_AU_comment = | Dependence_liability = | AdminRoutes = | Bioavail = | ProteinBound = | Metabolism = | Metabolites = | OnsetOfAction = | HalfLife = | DurationOfAction = | Excretion = }} |Section7={{Chembox Hazards | GHSPictograms = {{gHS skull and crossbones}} {{gHS health hazard}} | GHSSignalWord = '''DANGER''' | HPhrases = {{h-phrases|300|350|360}} | PPhrases = {{p-phrases|301+310|308+313}} | LD50 = 20 mg kg<sup>−1</sup> <small>(oral, rat)</small> }} |Section8={{Chembox Related | OtherFunction_label = ureas | OtherFunction = 1,3-Dimethylurea | OtherCompounds = {{unbulleted list|Noxytiolin|1,1,3,3-Tetramethylguanidine|Metformin|Allantoic acid|Buformin}} }} }} {{Infobox drug | drug_name = | INN = | type = <!-- empty --> | image = | width = | alt = | caption =
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'''Carmustine''', sold under the brand name '''BiCNU''' among others, is a medication used mainly for chemotherapy. It is a nitrogen mustard β-chloro-nitrosourea compound used as an alkylating agent.<ref>{{cite book | vauthors = Silverman RB, Holladay MW | chapter = Chapter 6 - DNA-Interactive Agents |date= January 2014 | title = The Organic Chemistry of Drug Design and Drug Action | edition = Third |pages=275–331 | veditors = Silverman RB, Holladay MW |place=Boston |publisher=Academic Press |language=en |doi=10.1016/b978-0-12-382030-3.00006-4 |isbn=978-0-12-382030-3 }}</ref>
==Description== Carmustine is an orange-yellow solid medication used mainly for chemotherapy. It is a nitrogen mustard β-chloro-nitrosourea compound.<ref>{{cite book | vauthors = Rider BJ | chapter = Carmustine |date= January 2007 | veditors = Enna SJ, Bylund DB | title = xPharm: The Comprehensive Pharmacology Reference |pages=1–4 |place=New York |publisher=Elsevier |language=en |doi=10.1016/b978-008055232-3.61389-3 |isbn=978-0-08-055232-3 }}</ref>
==Mechanism of action== As an alkylating agent, carmustine can form interstrand crosslinks in DNA, which prevents DNA replication and DNA transcription.<ref>{{Citation |title=NLM PubChem CID Index |work=Vitamin D Handbook |year=2007 |pages=239–244 |place=Hoboken, NJ, USA |publisher=John Wiley & Sons, Inc. |doi=10.1002/9780470238165.indsp1 |isbn=9780470238165 |doi-access=free }}</ref>
==Uses== Carmustine is used as an alkylating agent to treat several types of brain cancer including glioma, glioblastoma multiforme, medulloblastoma and astrocytoma, multiple myeloma, and lymphoma (Hodgkin's and non-Hodgkin).
Carmustine is sometimes used in conjunction with alkyl guanine transferase (AGT) inhibitors, such as ''O''<sup>6</sup>-benzylguanine. The AGT-inhibitors increase the efficacy of carmustine by inhibiting the direct reversal pathway of DNA repair, which will prevent formation of the interstrand crosslink between the N<sup>1</sup> of guanine and the N<sup>3</sup> of cytosine.
It is also used as part of a chemotherapeutic protocol in preparation for hematological stem cell transplantation, a type of bone marrow transplant, in order to reduce the white blood cell count in the recipient.<ref>{{cite journal | vauthors = Damaj G, Cornillon J, Bouabdallah K, Gressin R, Vigouroux S, Gastinne T, Ranchon F, Ghésquières H, Salles G, Yakoub-Agha I, Gyan E | title = Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review | journal = Bone Marrow Transplantation | volume = 52 | issue = 7 | pages = 941–949 | date = July 2017 | pmid = 28112752 | doi = 10.1038/bmt.2016.340 | doi-access = free }}</ref> Use under this protocol, usually with fludarabine and melphalan, was developed by oncologists at the University of Texas MD Anderson Cancer Center.{{citation needed|date=February 2018}}
==Implants== In the treatment of brain tumours, the U.S. Food and Drug Administration (FDA) approved biodegradable discs infused with carmustine (Gliadel).<ref name="pmid17575228">{{cite journal | vauthors = Ewend MG, Brem S, Gilbert M, Goodkin R, Penar PL, Varia M, Cush S, Carey LA | title = Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control | journal = Clinical Cancer Research | volume = 13 | issue = 12 | pages = 3637–3641 | date = June 2007 | pmid = 17575228 | doi = 10.1158/1078-0432.CCR-06-2095 | doi-access = | s2cid = 14016432 }}</ref> They are implanted under the skull during a surgery called a craniotomy. The disc allows for controlled release of carmustine in the extracellular fluid of the brain, thus eliminating the need for the encapsulated drug to cross the blood-brain barrier.<ref>{{cite web|url=http://www.hopkinsmedicine.org/hmn/W05/feature3.cfm|title=Hopkins Medicine Magazine - In Spite of All Odds|access-date=2014-07-08|archive-url=https://web.archive.org/web/20141120001145/http://www.hopkinsmedicine.org/hmn/W05/feature3.cfm|archive-date=2014-11-20|url-status=dead}}</ref>
==Production== Carmustine for injection was marketed under the name BiCNU by Bristol-Myers Squibb<ref>{{cite web|url=https://www.bms.com/life-and-science.html |title=Company Statement on BiCNU® (carmustine for injection) | publisher = Bristol-Myers Squibb Company |access-date=2015-01-31 |url-status=dead |archive-url=https://web.archive.org/web/20140711101801/https://www.bms.com/life-and-science.html |archive-date=2014-07-11 }}</ref> and now{{when|date=December 2017}} by Emcure Pharmaceuticals.<ref>{{Cite web |url=http://www.emcure.co.in/news/docs/BiCNU%20Emcure%20press%20release.pdf |title=Emcure Press release |access-date=2015-01-31 |archive-url=https://web.archive.org/web/20140702050137/http://emcure.co.in/news/docs/BiCNU%20Emcure%20press%20release.pdf |archive-date=2014-07-02 |url-status=dead }}</ref> In India it is sold under various brand names, including Consium.{{citation needed|date=December 2017}}. The product is available as a generic version with other manufacturers offering the product licensed in the US and EU markets.{{citation needed|date=February 2021}}
== See also == *Bendamustine *Lomustine *Semustine
== References == {{reflist}}
== External links == * {{cite web | title=Carmustine Implant | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a611045.html }}
{{Chemotherapeutic agents}} {{Portal bar | Medicine}}
Category:Orphan drugs Category:Ureas Category:Nitrosoureas Category:Alkylating antineoplastic agents Category:IARC Group 2A carcinogens Category:Cancer treatments Category:Chloroethyl compounds X