|Accession Number||DB00888 (APRD00249)|
A vesicant and necrotizing irritant destructive to mucous membranes, mechlorethamine is an alkylating drug. 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]
The FDA granted marketing approval for the orphan drug Valchlor (mechlorethamine) gel on August 23, 2013 for the topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (CTCL) in patients who have received prior skin-directed therapy. Each tube of Valchlor contains 0.016% of mechlorethamine which is equivalent to 0.02% mechlorethamine HCL.
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
|International Brands||Not Available|
|Brand mixtures||Not Available|
|Weight||Average: 156.054 |
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.
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.
Partially absorbed following intracavitary administration, most likely due to rapid deactivation by body fluids. When it is topically administered, systemic exposure was undetectable.
|Volume of distribution||Not Available|
|Protein binding||Not Available|
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|
Symptoms of overexposure include severe leukopenia, anemia, thrombocytopenia, and a hemorrhagic diathesis with subsequent delayed bleeding may develop. Death may follow. The most common adverse reactions (≥5%) of the topical formulation are dermatitis, pruritus, bacterial skin infection, skin ulceration or blistering, and hyperpigmentation. The oral LD50 for a rat is 10 mg/kg.
|Pharmacogenomic Effects/ADRs||Not Available|
|Food Interactions||Not Available|
Paul Siedlecki, "Preparation of nitrogen mustard derivatives." U.S. Patent US20030162990, issued August 28, 2003.US20030162990
|General References||Not Available|
|ATC Codes||L01AA05 — Chlormethine|
|PDB Entries||Not Available|
|FDA label||Download (306 KB)|
|MSDS||Download (37.2 KB)|
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|Predicted ADMET features|
|Mass Spec (NIST)||Download (8.14 KB)|
|Description||This compound belongs to the class of organic compounds known as nitrogen mustard compounds. These are compounds having two beta-haloalkyl groups bound to a nitrogen atom.|
|Super Class||Organic nitrogen compounds|
|Sub Class||Nitrogen mustard compounds|
|Direct Parent||Nitrogen mustard compounds|
|Alternative Parents||Trialkylamines / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives / Alkyl chlorides|
|Substituents||Nitrogen mustard / Tertiary aliphatic amine / Tertiary amine / Organopnictogen compound / Hydrocarbon derivative / Organochloride / Organohalogen compound / Amine / Alkyl halide / Alkyl chloride|
|Molecular Framework||Aliphatic acyclic compounds|
|External Descriptors||organochlorine compound, nitrogen mustard (CHEBI:28925 )|
- Pharmacological action
- General Function:
- Used for biological information storage.
- Specific Function:
- DNA contains the instructions needed for an organism to develop, survive and reproduce.
- Molecular Weight:
- 2.15 x 1012 Da
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
- 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:17016423 ]
- 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:15781216 ]
- 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. doi: 10.1021/tx900078y. [PubMed:19480393 ]