Carmustine

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Carmustine
Carmustine.svg
Carmustine ball-and-stick.png
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 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 205-838-2
KEGG
MeSH Carmustine
PubChem CID
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) Yes check.svgY
    Key: DLGOEMSEDOSKAD-UHFFFAOYSA-N Yes check.svgY
  • C(CCl)NC(=O)N(CCCl)N=O
Properties
C5H9Cl2N3O2
Molar mass 214.05 g·mol−1
AppearanceOrange 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:
GHS-pictogram-skull.svg GHS-pictogram-silhouette.svg
Danger
H300, H350, H360
P301+P310, P308+P313
Lethal dose or concentration (LD, LC):
20 mg kg−1(oral, rat)
Related compounds
Related ureas
 1,3-Dimethylurea
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)
Carmustine
Clinical data
Trade names BiCNU, Gliadel
AHFS/Drugs.com Monograph
MedlinePlus a682060
License data
Drug class Antineoplastic agents
Legal status
Legal status
Identifiers
CompTox Dashboard (EPA)
ECHA InfoCard 100.005.309 OOjs UI icon edit-ltr-progressive.svg

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.[ citation needed ]

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[ when? ] by Emcure Pharmaceuticals. [14] In India it is sold under various brand names, including Consium.[ citation needed ]. The product is available as a generic version with other manufacturers offering the product licensed in the US and EU markets.[ citation needed ]

See also

Related Research Articles

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<span class="mw-page-title-main">Nitrogen mustard</span> Family of chemical compounds

Nitrogen mustards (NMs) are cytotoxic organic compounds with the bis(2-chloroethyl)amino ((ClC2H4)2NR) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen mustards are nonspecific DNA alkylating agents.

<span class="mw-page-title-main">Melphalan</span> Chemical compound

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<span class="mw-page-title-main">Nitrosourea</span> Chemical compound

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Platinum-based antineoplastic drugs are chemotherapeutic agents used to treat cancer. Their active moieties are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for cancer. In this form of chemotherapy, commonly used drugs include cisplatin, oxaliplatin, and carboplatin, but several have been proposed or are under development. Addition of platinum-based chemotherapy drugs to chemoradiation in women with early cervical cancer seems to improve survival and reduce risk of recurrence.

Arabinopyranosyl-<i>N</i>-methyl-<i>N</i>-nitrosourea Chemical compound

Arabinopyranosyl-N-methyl-N-nitrosourea, also known as Aranose (Араноза) is a cytostatic anticancer chemotherapeutic drug of an alkylating type. Chemically it is a nitrosourea derivative. It was developed in the Soviet Union in the 1970s. It was claimed by its developers that its advantages over other nitrosoureas are a relatively low hematological toxicity and a wider therapeutic index, which allows for its outpatient administration.

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 (January 2007). "Carmustine". In Enna SJ, Bylund DB (eds.). 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.
  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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