Carmustine

Carmustine
Names
	IUPAC name 1,3-Bis(2-chloroethyl)-1-nitrosourea
	Other names N,N’-Bis(2-chloroethyl)-N-nitrosourea
Identifiers
CAS Number	154-93-8 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:3423 ;
ChEMBL	ChEMBL513 ;
ChemSpider	2480 ;
DrugBank	DB00262 ;
ECHA InfoCard	100.005.309
EC Number	205-838-2;
KEGG	D00254 ;
MeSH	Carmustine
PubChem CID	2578;
RTECS number	YS2625000;
UNII	U68WG3173Y ;
UN number	2811
CompTox Dashboard (EPA)	DTXSID8022743 ;
	InChI InChI=1S/C5H9Cl2N3O2/c6-1-3-8-5(11)10(9-12)4-2-7/h1-4H2,(H,8,11) Key: DLGOEMSEDOSKAD-UHFFFAOYSA-N ;
	SMILES ClCCNC(=O)N(CCCl)N=O;
Properties
Chemical formula	C5H9Cl2N3O2
Molar mass	214.05 g·mol−1
Appearance	Orange crystals
Odor	Odourless
Melting point	30 °C (86 °F; 303 K)
log P	1.375
Acidity (pKa)	10.194
Basicity (pKb)	3.803
Pharmacology
ATC code	L01AD01 (WHO)
Hazards
	GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H300, H350, H360
Precautionary statements	P301+P310, P308+P313
	Lethal dose or concentration (LD, LC):
LD50 (median dose)	20 mg kg−1 (oral, rat)
Related compounds
Related ureas	Dimethylurea
Related compounds	Noxytiolin; 1,1,3,3-Tetramethylguanidine; Metformin; Allantoic acid; Buformin;
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Carmustine (bis-chloroethylnitrosourea, BCNU, BiCNU) is a medication used mainly for chemotherapy. It is a nitrogen mustard β-chloro-nitrosourea compound used as an alkylating agent.

Description

Carmustine is an orange-yellow solid medication used mainly for chemotherapy. It is a nitrogen mustard β-chloro-nitrosourea compound .

Mechanism of action

As a dialkylating agent, carmustine can form interstrand crosslinks in DNA, which prevents DNA replication and DNA transcription.^{[citation needed]}

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).

BCNU is sometimes used in conjunction with alkyl guanine transferase (AGT) inhibitors, such as O⁶-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 N¹ of guanine and the N³ 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.^[2] Use under this protocol, usually with fludarabine and melphalan, was developed by oncologists at the University of Texas MD Anderson Cancer Center.^{[citation needed]}

Implants

In the treatment of brain tumours, the U.S. Food and Drug Administration (FDA) approved biodegradable discs infused with carmustine (Gliadel).^[3] 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.^[4]

Production

Carmustine for injection was marketed under the name BiCNU by Bristol-Myers Squibb^[5] and now^[when?] by Emcure Pharmaceuticals.^[6] In India it is sold under various brand names, including Consium.^{[citation needed]}

References

^ CID 2578 from PubChem
^ Damaj, G; Cornillon, J; Bouabdallah, K; Gressin, R; Vigouroux, S; Gastinne, T; Ranchon, F; Ghésquières, H; Salles, G; Yakoub-Agha, I; Gyan, E (2017). "Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: A review". Bone Marrow Transplantation. 52 (7): 941–949. doi:10.1038/bmt.2016.340. PMID 28112752.
^ Ewend MG, Brem S, Gilbert M, et al. (June 2007). "Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control". Clin. Cancer Res. 13 (12): 3637–41. doi:10.1158/1078-0432.CCR-06-2095. PMID 17575228.
^ "Hopkins Medicine Magazine - In Spite of All Odds".
^ "Archived copy". Archived from the original on 2014-07-11. Retrieved 2015-01-31. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)CS1 maint: archived copy as title (link)
^ "Emcure Press release" (PDF). Archived from the original (PDF) on 2014-07-02. Retrieved 2015-01-31. {{cite web}}: Unknown parameter |dead-url= ignored (|url-status= suggested) (help)

External links

[1] CID 2578 from PubChem

[2] Damaj, G; Cornillon, J; Bouabdallah, K; Gressin, R; Vigouroux, S; Gastinne, T; Ranchon, F; Ghésquières, H; Salles, G; Yakoub-Agha, I; Gyan, E (2017). "Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: A review". Bone Marrow Transplantation. 52 (7): 941–949. doi:10.1038/bmt.2016.340. PMID 28112752.

[pmid17575228-3] Ewend MG, Brem S, Gilbert M, et al. (June 2007). "Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control". Clin. Cancer Res. 13 (12): 3637–41. doi:10.1158/1078-0432.CCR-06-2095. PMID 17575228.

[4] "Hopkins Medicine Magazine - In Spite of All Odds".

[5] "Archived copy". Archived from the original on 2014-07-11. Retrieved 2015-01-31. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)CS1 maint: archived copy as title (link)

[6] "Emcure Press release" (PDF). Archived from the original (PDF) on 2014-07-02. Retrieved 2015-01-31. {{cite web}}: Unknown parameter |dead-url= ignored (|url-status= suggested) (help)

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