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Identification
Name Mechlorethamine
Accession Number DB00888 (APRD00249)
Type small molecule
Groups approved
Description

A vesicant and necrotizing irritant destructive to mucous membranes. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkin's disease and lymphomas. It causes severe gastrointestinal and bone marrow damage. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Chlorethazine
Chlormethine
HN2
MBA
Mechloroethamine
Mecloretamina
Mustine
Nitrogen mustard
Salts Not Available
Brand names
Name Company
Caryolysin
Caryolysine
Cloramin
Dichloren
Embichin
Mustargen
Mutagen
Brand mixtures Not Available
Categories
  • Alkylating Agents
  • Antineoplastic Agents, Alkylating
  • Irritants
  • Chemical Warfare Agents
CAS number 51-75-2
Weight Average: 156.054
Monoisotopic: 155.026854771
Chemical Formula C5H11Cl2N
InChI Key InChIKey=HAWPXGHAZFHHAD-UHFFFAOYSA-N
InChI
InChI=1S/C5H11Cl2N/c1-8(4-2-6)5-3-7/h2-5H2,1H3
Plain Text
IUPAC Name
bis(2-chloroethyl)(methyl)amine
SMILES
CN(CCCl)CCCl
Plain Text
Mass Spec show (8.14 KB)
Taxonomy
Kingdom Organic
Classes
  • Nitrogen Mustards
Substructures
  • Aliphatic and Aryl Amines
  • Alkyl Halides
  • Nitrogen Mustards
Pharmacology
Indication For the palliative treatment of Hodgkin's disease (Stages III and IV), lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia, polycythemia vera, mycosis fungoides, and bronchogenic carcinoma. Also for the palliative treatment of metastatic carcinoma resulting in effusion.
Pharmacodynamics Mechlorethamine also known as mustine, nitrogen mustard, and HN2, is the prototype anticancer chemotherapeutic drug. Successful clinical use of mechlorethamine gave birth to the field of anticancer chemotherapy. The drug is an analogue of mustard gas and was derived from toxic gas warfare research. It belongs to the group of nitrogen mustard alkylating agents. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
Mechanism of action Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. Mechlorethamine is cell cycle phase-nonspecific.
Absorption Partially absorbed following intracavitary administration, most likely due to rapid deactivation by body fluids.
Volume of distribution Not Available
Protein binding Not Available
Metabolism Undergoes rapid chemical transformation and combines with water or reactive compounds of cells, so that the drug is no longer present in active form a few minutes after administration.
Route of elimination Not Available
Half life 15 minutes
Clearance Not Available
Toxicity Symptoms of overexposure include severe leukopenia, anemia, thrombocytopenia, and a hemorrhagic diathesis with subsequent delayed bleeding may develop. Death may follow. The intravenous LD50 is 2 mg/kg and 1.6 mg/kg in mouse and rat, respectively.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Lundbeck inc
Packagers
Dosage forms
Form Route Strength
Injection, powder, for solution Intravenous
Powder Topical
Prices
Unit description Cost Unit
Mustargen 10 mg vial 178.71 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point -60 °C PhysProp
boiling point 87 °C at 1.80E+01 mm Hg PhysProp
water solubility 1.2E+004 mg/L (at 25 °C) BEILSTEIN
logP 0.91 SELASSIE,CD ET AL. (1990)
pKa 6.43 (at 25 °C) PERRIN,DD (1965)
Predicted Properties
Property Value Source
water solubility 3.34e+01 g/l ALOGPS
logP 1.31 ALOGPS
logP 1.52 ChemAxon
logS -0.67 ALOGPS
pKa (strongest basic) 6.08 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 3.24 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 38.67 ChemAxon
polarizability 15.84 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07115 Link_out
PubChem Compound 4033 Link_out
PubChem Substance 46505784 Link_out
ChemSpider 3893 Link_out
ChEBI 28925 Link_out
ChEMBL 28925 Link_out
Therapeutic Targets Database DAP000790 Link_out
PharmGKB PA450336 Link_out
Drug Product Database 16063 Link_out
RxList http://www.rxlist.com/cgi/generic3/mustargen.htm Link_out
Drugs.com http://www.drugs.com/cdi/mechlorethamine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Mechlorethamine Link_out
ATC Codes
  • L01AA05
  • D08AX04
AHFS Codes
  • 84:04.92
  • 10:00.00
PDB Entries Not Available
FDA label Not Available
MSDS show (51.6 KB)
Interactions
Drug Interactions
Drug Interaction
Bendamustine Increases toxicity through pharmacodynamic synergism. Additive myelosuppression.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available
Targets

1. DNA

Pharmacological action: yes
Actions: intercalation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. De Alencar TA, Leitao AC, Lage C: Nitrogen mustard- and half-mustard-induced damage in Escherichia coli requires different DNA repair pathways. Mutat Res. 2005 Apr 4;582(1-2):105-15. Pubmed
  4. Loeber RL, Michaelson-Richie ED, Codreanu SG, Liebler DC, Campbell CR, Tretyakova NY: Proteomic analysis of DNA-protein cross-linking by antitumor nitrogen mustards. Chem Res Toxicol. 2009 Jun;22(6):1151-62. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19