T3DB: Mechlorethamine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (1)XML

Targets (1)

Record Information

Version

2.0

Creation Date

2014-08-29 05:52:43 UTC

Update Date

2014-12-24 20:26:42 UTC

Accession Number

T3D4204

Identification

Common Name

Mechlorethamine

Class

Small Molecule

Description

Mechlorethamine is only found in individuals that have used or taken this drug. It is 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. 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.

Compound Type

Alkylating Agent
Amine
Antineoplastic Agent, Alkylating
Chemical Warfare Agent
Cigarette Toxin
Drug
Irritant
Metabolite
Organic Compound
Organochloride
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
2,2'-dichloro-N-methyldiethylamine
beta,Beta'-dichlorodiethyl-N-methylamine
Bis(2-chloroethyl)methylamine
Bis(beta-chloroethyl)methylamine
Chlorethazine
Chlormethine
HN2
MBA
Mechloroethamine
Mecloretamina
Methylbis(2-chloroethyl)amine
Methylbis(beta-chloroethyl)amine
Mustargen
Mustine
N-methyl-bis(2-chloroethyl)amine
N-Methyl-bis(beta-chloroethyl)amine
Nitrogen mustard
Valchlor
β,β'-dichlorodiethyl-N-methylamine

Chemical Formula

C₅H₁₁Cl₂N

Average Molecular Mass

156.054 g/mol

Monoisotopic Mass

155.027 g/mol

CAS Registry Number

51-75-2

IUPAC Name

bis(2-chloroethyl)(methyl)amine

Traditional Name

mechlorethamine

SMILES

CN(CCCl)CCCl

InChI Identifier

InChI=1S/C5H11Cl2N/c1-8(4-2-6)5-3-7/h2-5H2,1H3

InChI Key

InChIKey=HAWPXGHAZFHHAD-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as nitrogen mustard compounds. Nitrogen mustard compounds are compounds having two beta-haloalkyl groups bound to a nitrogen atom.

Kingdom

Organic compounds

Super Class

Organic nitrogen compounds

Class

Organonitrogen compounds

Sub Class

Nitrogen mustard compounds

Direct Parent

Nitrogen mustard compounds

Alternative Parents

Substituents

Nitrogen mustard
Tertiary aliphatic amine
Tertiary amine
Organopnictogen compound
Hydrocarbon derivative
Organochloride
Organohalogen compound
Amine
Alkyl halide
Alkyl chloride
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

organochlorine compound (CHEBI:28925 )
nitrogen mustard (CHEBI:28925 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

alkylating agent

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	108 - 110°C
Boiling Point	87°C at 1.80E+01 mm Hg
Solubility	Very soluble
LogP	0.91

Predicted Properties

Property	Value	Source
Water Solubility	33.4 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 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	38.67 m³·mol⁻¹	ChemAxon
Polarizability	15.84 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4l-9400000000-37f4081d8c3fd8e974c6	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0900000000-2282bef263bfa8a41123	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a4i-7900000000-b0b770790e86670fc2a5	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-03di-9000000000-5d96975a96ed8783c02e	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udi-1900000000-7801c92cb7dc490c200d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0uxr-4900000000-0df7677828ba3d2293ad	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-08i3-9100000000-67d0e475a21ed8a44dca	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0900000000-b39c5053cfb605f67e08	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-08fr-9400000000-9836caddbb3ebb21e8bb	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-03di-9000000000-dcc5bf7c33b77979d5a5	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0ue9-8900000000-60357d33a598f0fa346f	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-001i-9000000000-c2fa753da65a4bac80a1	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-001i-9000000000-c2fa753da65a4bac80a1	2021-10-11	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0a4i-7900000000-66a0ef3007bd03bd9367	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum

Toxicity Profile

Route of Exposure

Partially absorbed following intracavitary administration, most likely due to rapid deactivation by body fluids. When it is topically administered, systemic exposure was undetectable.

Mechanism of Toxicity

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.

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. Half Life: 15 minutes

Toxicity Values

The oral LD50 for a rat is 10 mg/kg.

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

Chlormethine is probably carcinogenic to humans (Group 2A). Chlormethine is part of MOPP, a combination chemotherapy regimen that is carcinogenic to humans (Group 1). (2)

Uses/Sources

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.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

28925

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Mechlorethamine

References

Synthesis Reference

Paul Siedlecki, “Preparation of nitrogen mustard derivatives.” U.S. Patent US20030162990, issued August 28, 2003.

MSDS

Link

General References

FDA label
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

1. DNA

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

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [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. [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. [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. [19480393 ]

Mechlorethamine (T3D4204)

Structure for T3D4204: Mechlorethamine

Targets

References