View source for Chemistry:Carmustine

{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 487305398
| ImageFile = Carmustine.svg
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageName = Skeletal formula of carmustine
| ImageFile1 = Carmustine ball-and-stick.png
| 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
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| INN_EMA = 
| Licence_US = 
| Legal_status = 
| Legal_AU = S4
| Legal_AU_comment = 
| Legal_CA = 
| Legal_CA_comment = 
| Legal_NZ = 
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| 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
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| Pregnancy_AU = D
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|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 = [[Chemistry:Dimethylurea|Dimethylurea]]
| OtherCompounds = {{unbulleted list|[[Chemistry:Noxytiolin|Noxytiolin]]|[[Chemistry:1,1,3,3-Tetramethylguanidine|1,1,3,3-Tetramethylguanidine]]|[[Chemistry:Metformin|Metformin]]|[[Chemistry:Allantoic acid|Allantoic acid]]|[[Chemistry:Buformin|Buformin]]}}
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}}
{{Infobox drug
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| INN               = 
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<!-- Clinical data -->
| pronounce         = 
| tradename         = BiCNU, Gliadel
| Drugs.com         = {{drugs.com|monograph|carmustine}}
| MedlinePlus       = a682060
| licence_EU        = <!-- EMA uses INN (or special INN_EMA) -->
| DailyMedID        = Carmustine
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'''Carmustine''', sold under the brand name '''BiCNU''' among others, is a [[Chemistry:Medication|medication]] used mainly for [[Medicine:Chemotherapy|chemotherapy]]. It is a [[Chemistry:Nitrogen mustard|nitrogen mustard]] β-chloro-nitrosourea compound used as an [[Chemistry:Alkylating antineoplastic agent|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 [[Medicine:Chemotherapy|chemotherapy]]. It is a [[Chemistry:Nitrogen mustard|nitrogen mustard]] β-chloro-nitrosourea compound.<ref>{{Citation |last=Rider |first=Barbara J. |title=Carmustine |date=2007-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780080552323613893 |work=xPharm: The Comprehensive Pharmacology Reference |pages=1–4 |editor-last=Enna |editor-first=S. J. |place=New York |publisher=Elsevier |language=en |doi=10.1016/b978-008055232-3.61389-3 |isbn=978-0-08-055232-3 |access-date=2022-03-29 |editor2-last=Bylund |editor2-first=David B.}}</ref>

==Mechanism of action==
As an [[Chemistry:Alkylation|alkylating agent]], carmustine can form interstrand crosslinks in [[Biology:DNA|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 [[Chemistry:Alkylating antineoplastic agent|alkylating agent]] to treat several types of brain cancer including glioma, glioblastoma multiforme, [[Medicine:Medulloblastoma|medulloblastoma]] and astrocytoma, [[Medicine:Multiple myeloma|multiple myeloma]], and [[Medicine:Lymphoma|lymphoma]] ([[Medicine:Hodgkin's lymphoma|Hodgkin's]] and [[Medicine:Non-Hodgkin lymphoma|non-Hodgkin]]).

Carmustine is sometimes used in conjunction with alkyl guanine transferase (AGT) inhibitors, such as [[Chemistry:O6-Benzylguanine|''O''<sup>6</sup>-benzylguanine]]. The AGT-inhibitors increase the efficacy of carmustine by inhibiting the [[Biology:DNA repair#Direct reversal|direct reversal pathway]] of DNA repair, which will prevent formation of the [[Biology:Crosslinking of DNA|interstrand crosslink]] between the N<sup>1</sup> of [[Chemistry:Guanine|guanine]] and the N<sup>3</sup> of [[Chemistry:Cytosine|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 | display-authors = 6 | 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 [[Chemistry:Fludarabine|fludarabine]] and [[Chemistry:Melphalan|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. [[Organization:Food and Drug Administration|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 | display-authors = 6 | 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 ==
*[[Chemistry:Bendamustine|Bendamustine]]
*[[Chemistry:Lomustine|Lomustine]]
*[[Chemistry:Semustine|Semustine]]

== References ==
{{reflist}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/carmustine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Carmustine }}
* {{cite web | title=Carmustine Implant | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a611045.html }}

{{Chemotherapeutic agents}}

[[Category:Orphan drugs]]
[[Category:Ureas]]
[[Category:Nitrosoureas]]
[[Category:Alkylating antineoplastic agents]]
[[Category:IARC Group 2A carcinogens]]
[[Category:Organochlorides]]
[[Category:Cancer treatments]]
[[Category:Chloroethyl compounds]]

{{Sourceattribution|Carmustine}}