Carmustine
Skeletal formula of carmustine
Ball-and-stick model of carmustine molecule
Names
IUPAC name
1,3-Bis(2-chloroethyl)-1-nitrosourea[1]
Other names
N,N'-Bis(2-chloroethyl)-N-nitrosourea, bis-chloroethylnitrosourea, BCNU
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.005.309
EC Number
  • 205-838-2
KEGG
MeSH Carmustine
RTECS number
  • YS2625000
UNII
UN number 2811
  • InChI=1S/C5H9Cl2N3O2/c6-1-3-8-5(11)10(9-12)4-2-7/h1-4H2,(H,8,11) checkY
    Key: DLGOEMSEDOSKAD-UHFFFAOYSA-N checkY
  • C(CCl)NC(=O)N(CCCl)N=O
Properties
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
L01AD01 (WHO)
  • AU: D
License data
Legal status
Hazards
GHS labelling:
GHS06: Toxic GHS08: Health hazard
Danger
H300, H350, H360
P301+P310, P308+P313
Lethal dose or concentration (LD, LC):
20 mg kg−1 (oral, rat)
Related compounds
Related ureas
 Dimethylurea
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)
Infobox references
Carmustine
Clinical data
Trade namesBiCNU, Gliadel
AHFS/Drugs.comMonograph
MedlinePlusa682060
License data
Drug classAntineoplastic agents
Legal status
Legal status
Identifiers
CompTox Dashboard (EPA)
ECHA InfoCard100.005.309

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.[7]

Description

Carmustine is an orange-yellow solid medication used mainly for chemotherapy. It is a nitrogen mustard β-chloro-nitrosourea compound.[8]

Mechanism of action

As an alkylating agent, carmustine can form interstrand crosslinks in DNA, which prevents DNA replication and DNA transcription.[9]

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 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.[10] Use under this protocol, usually with fludarabine and melphalan, was developed by oncologists at the University of Texas MD Anderson Cancer Center.

Implants

In the treatment of brain tumours, the U.S. Food and Drug Administration (FDA) approved biodegradable discs infused with carmustine (Gliadel).[11] 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.[12]

Production

Carmustine for injection was marketed under the name BiCNU by Bristol-Myers Squibb[13] and now by Emcure Pharmaceuticals.[14] In India it is sold under various brand names, including Consium.. The product is available as a generic version with other manufacturers offering the product licensed in the US and EU markets.

See also

References

  1. ↑ CID 2578 from PubChem
  2. ↑ "Carmustine 100mg Powder and solvent for Solution for Infusion - Summary of Product Characteristics (SmPC)". (emc). 24 March 2020.
  3. ↑ "Gliadel 7.7mg Implant - Summary of Product Characteristics (SmPC)". (emc). 15 June 2020.
  4. ↑ "Bicnu- carmustine kit". DailyMed. Retrieved 27 February 2021.
  5. ↑ "Gliadel- carmustine wafer". DailyMed. Retrieved 27 February 2021.
  6. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  7. ↑ Silverman RB, Holladay MW (January 2014). "Chapter 6 - DNA-Interactive Agents". In Silverman RB, Holladay MW (eds.). The Organic Chemistry of Drug Design and Drug Action (Third ed.). Boston: Academic Press. pp. 275–331. doi:10.1016/b978-0-12-382030-3.00006-4. ISBN 978-0-12-382030-3.
  8. ↑ Rider BJ (2007-01-01), Enna SJ, Bylund DB (eds.), "Carmustine", xPharm: The Comprehensive Pharmacology Reference, New York: Elsevier, pp. 1–4, doi:10.1016/b978-008055232-3.61389-3, ISBN 978-0-08-055232-3, retrieved 2022-03-29
  9. ↑ "NLM PubChem CID Index", Vitamin D Handbook, Hoboken, NJ, USA: John Wiley & Sons, Inc., pp. 239–244, 2007, doi:10.1002/9780470238165.indsp1, ISBN 9780470238165
  10. ↑ Damaj G, Cornillon J, Bouabdallah K, Gressin R, Vigouroux S, Gastinne T, et al. (July 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.
  11. ↑ Ewend MG, Brem S, Gilbert M, Goodkin R, Penar PL, Varia 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". Clinical Cancer Research. 13 (12): 3637–3641. doi:10.1158/1078-0432.CCR-06-2095. PMID 17575228. S2CID 14016432.
  12. ↑ "Hopkins Medicine Magazine - In Spite of All Odds". Archived from the original on 2014-11-20. Retrieved 2014-07-08.
  13. ↑ "Company Statement on BiCNU® (carmustine for injection)". Bristol-Myers Squibb Company. Archived from the original on 2014-07-11. Retrieved 2015-01-31.
  14. ↑ "Emcure Press release" (PDF). Archived from the original (PDF) on 2014-07-02. Retrieved 2015-01-31.
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