Semustin

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Structural formula
Semustine's structural formula
Structure without stereochemistry
General
Non-proprietary name Semustin
other names
  • Methyllomustine
  • 4-methyllomustine
  • Methyl CCNU
  • MeCCNU
  • NSC 95441
  • 1- (2-chloroethyl) -3- (4-methylcyclohexyl) -1-nitrosourea ( IUPAC )
Molecular formula C 10 H 18 ClN 3 O 2
External identifiers / databases
CAS number 13909-09-6
EC number 634-275-9
ECHA InfoCard 100.162.271
PubChem 5198
Wikidata Q1230937
Drug information
ATC code

L01 AD03

Drug class

Cytostatic

properties
Molar mass 247.72 g mol −1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
06 - Toxic or very toxic 08 - Dangerous to health

danger

H and P phrases H: 300-311-315-319-331-335-350-360
P: 201-261-264-280-301 + 310-305 + 351 + 338
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Semustine (synonym: Me thyl- C hlorethyl- C yclohexyl- N itroso- U rea = MeCCNU ), chemically 1- (2-chloroethyl) -3- (4-methylcyclohexyl) -1-nitrosourea , which is non-proprietary name for a cytostatic agent from the group of nitrosoureas . It is the 4-methyl derivative of lomustine .

Chemical properties

Stereochemistry

Semustine is a compound of which two isomers , so-called cis / trans isomers, exist due to the different substitution options on the cyclohexane ring . These isomers can differ in certain physical properties and physiological effects. The individual compounds can be isolated in a targeted manner by means of suitable synthesis strategies or separation processes.

The following important information is missing from this article or section:
Which isomer / isomer mixture is used medicinally?
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pharmacology

Mechanism of action

Semustine changed as all nitrosoureas the genetic material in the cell nuclei . As a result, the affected cells can no longer divide and die after a while. The genome damage mainly affects rapidly dividing cells - especially cancer cells. Semustine is able to cross the blood-brain barrier . This is beneficial in the treatment of melanoma with CNS metastatisation.

Side effects

Semustine is myelotoxic , which means it damages the bone marrow . This damage has a negative effect on blood formation, especially platelets and leukocytes . The main side effects are nausea and hair loss .

Like all nitrosoureas, Semustine is itself carcinogenic , i.e. carcinogenic. In animal experiments it increases the total tumor rate in rats after intraperitoneal administration and the rate of leukemia and malignant lymphomas in female mice . It has been classified as carcinogenic for humans since the early 1990s. The risk of developing leukemia increases significantly after treatment with Semustin.

Individual evidence

  1. ↑ a b Datasheet Semustine at Sigma-Aldrich , accessed on April 23, 2011 ( PDF ).
  2. ↑ Elizabeth K. Weisburger : Bioassay program for carcinogenic hazards of cancer chemotherapeutic agents. In: Cancer 40, 1977, S, 1935-1949, PMID 907995 .
  3. ↑ H. Tinwell and J. Ashby: Activity of the human carcinogen MeCCNU in the mouse bone marrow micronucleus assay. In: Environ Mol Mutagen 17, 1991, pp. 152-154, PMID 2022193 .
  4. ↑ JD Boice et al.: Leukemia and preleukemia after adjuvant treatment of gastrointestinal cancer with semustine (methyl-CCNU). In: NEJM 309, 1983, pp. 1079-1084, PMID 6353233 .

literature

  • 13th Report on Carcinogens (RoC): Nitrosourea Chemotherapeutic Agents ( 1- (2-Chloroethyl) -3- (4-Methylcyclohexyl) -1-Nitrosourea ) (PDF file; 233 kB)
  • Collective of authors: Radiation therapy and fluorouracil with or without semustine for the treatment of patients with surgical adjuvant adenocarcinoma of the rectum. Gastrointestinal Tumor Study Group. In: Journal of Clinical Oncology . 10, 1992, pp. 549-557. PMID 1548520
  • National Toxicology Program: 1- (2-Chloroethyl) -3- (4-methylcyclohexyl) -1-nitrosourea (MeCCNU). In: Rep Carcinog 10, 2002, pp. 53-54. PMID 15320318
  • RS Witte et al .: PALA versus streptozotocin, doxorubicin, and MeCCNU in the treatment of patients with advanced pancreatic carcinoma. In: Invest New Drugs 16, 1998-1999, pp. 315-318. PMID 10426663
  • JL Clark et al: Adjuvant 5-FU and MeCCNU improves survival following curative gastrectomy for adenocarcinoma. In: Am Surg 56, 1990. pp. 423-427. PMID 2368986
  • M. Willem: Adjuvant therapy for rectal cancer: is 5-FU effective without MeCCNU. In: Oncology (New York) 3, 1989, p. 11. PMID 2641312
  • RC Vyas et al: Genotoxic effects of MeCCNU on human peripheral blood lymphocytes. In: Toxicology Letters 44, 1988, pp. 153-159. PMID 3188073