MECHLORETHAMINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C5H11Cl2N
Molecular Weight	156.054
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(CCCl)CCCl

InChI

InChIKey=HAWPXGHAZFHHAD-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/19480393

Mechlorethamine also known as mustine, brand name MUSTARGEN administered intravenously is the prototype anticancer chemotherapeutic drug, is indicated 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. In 2013 was approved orphan drug Valchlor (mechlorethamine) gel 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. Mechlorethamine belongs to the group of nitrogen mustard alkylating agents. Alkylating agents work by three different mechanisms: attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, 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 all of which achieve the same end result - disruption of DNA function and cell death.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 247 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19480393	Crosslinking Agent 80

Conditions

Condition	Modality	Highest Phase	Product
Hodgkin's disease (Stages III and IV) 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8360	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date -6.5638079E11
Lymphosarcoma 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8360	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date -6.5638079E11
Chronic lymphocytic leukemia 59 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8360	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date -6.5638079E11
Chronic myelocytic leukemia 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8360	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date -6.5638079E11
Mycosis fungoides 30 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8360	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date -6.5638079E11

C_max

Value	Dose	Co-administered	Analyte	Population
1.72 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11129502	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		MECHLORETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3.17 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11129502	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		MECHLORETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.16 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11129502	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		MECHLORETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 14-80 n = 26 Health Status: unhealthy Condition: Reticulum cell sarcoma Age Group: 14-80 Sex: M+F Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	Disc. AE: Thrombocytopenia, Hemorrhage... AEs leading to discontinuation/dose reduction: Thrombocytopenia (severe, 3.8%) Hemorrhage (3.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 32-81 n = 18 Health Status: unhealthy Condition: Lymphosarcoma Age Group: 32-81 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	Disc. AE: Pancytopenia... AEs leading to discontinuation/dose reduction: Pancytopenia (5.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
0.02 % 1 times / day multiple, topical Recommended Dose: 0.02 %, 1 times / day Route: topical Route: multiple Dose: 0.02 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517	unhealthy, 44 n = 20 Health Status: unhealthy Condition: Psoriasis Age Group: 44 Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517	Disc. AE: Contact dermatitis... AEs leading to discontinuation/dose reduction: Contact dermatitis (75%) Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517
0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	Disc. AE: Eye injury, Dermatitis... AEs leading to discontinuation/dose reduction: Eye injury Dermatitis Cancer of skin (excl melanoma) Disorder fetal Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
0.4 mg/kg single, intravenous (total) Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Hodgkin's disease\| lymphosarcoma\|chronic myelocytic leukemia\| chronic lymphocytic leukemia\| polycythemia vera\| mycosis fungoides\|bronchogenic carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2	Disc. AE: Amyloidosis... AEs leading to discontinuation/dose reduction: Amyloidosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2

AEs

AE	Significance	Dose	Population
Hemorrhage	3.8% Disc. AE	0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 14-80 n = 26 Health Status: unhealthy Condition: Reticulum cell sarcoma Age Group: 14-80 Sex: M+F Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
Thrombocytopenia	severe, 3.8% Disc. AE	0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 14-80 n = 26 Health Status: unhealthy Condition: Reticulum cell sarcoma Age Group: 14-80 Sex: M+F Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
Pancytopenia	5.6% Disc. AE	0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 32-81 n = 18 Health Status: unhealthy Condition: Lymphosarcoma Age Group: 32-81 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
Contact dermatitis	75% Disc. AE	0.02 % 1 times / day multiple, topical Recommended Dose: 0.02 %, 1 times / day Route: topical Route: multiple Dose: 0.02 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517	unhealthy, 44 n = 20 Health Status: unhealthy Condition: Psoriasis Age Group: 44 Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517
Cancer of skin (excl melanoma)	Disc. AE	0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
Dermatitis	Disc. AE	0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
Disorder fetal	Disc. AE	0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
Eye injury	Disc. AE	0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
Amyloidosis	Disc. AE	0.4 mg/kg single, intravenous (total) Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Hodgkin's disease\| lymphosarcoma\|chronic myelocytic leukemia\| chronic lymphocytic leukemia\| polycythemia vera\| mycosis fungoides\|bronchogenic carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:28925	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28925
ZINC	ZINC000002539484	http://zinc15.docking.org/substances/ZINC000002539484
eMolecules	729204	https://www.emolecules.com/cgi-bin/more?vid=729204

PubMed

Title	Date	PubMed
A pilot study on the influence of a corticotropin (4-9) analogue on Vinca alkaloid-induced neuropathy.	1992 Oct	1329697
Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2.	2001 Aug	11763419
Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero.	2001 Dec	11779294
[Z-form of intraphage DNA].	2002	12534267
ABVD versus stanford V versus MEC in unfavourable Hodgkin's lymphoma: results of a randomised trial.	2002	12078888
Treatment of cutaneous T cell lymphoma: current status and future directions.	2002	11978140
Postpneumonectomy-like syndrome after chemoradiation therapy for lymphoma.	2002 Dec	12453864
An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.	2002 Dec 15	12467067
Biological effects of DNA damage in the hyperthermophilic archaeon Sulfolobus acidocaldarius.	2002 Feb 19	11934490
Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease.	2002 Feb 6	11830608
Subdiaphragmatic Hodgkin's disease: the University of Florida experience.	2002 Jan 1	11777634
Inhibition of nucleotide excision repair and sensitisation of cells to DNA cross-linking anticancer drugs by F 11782, a novel fluorinated epipodophylloid.	2002 Jan 15	11841800
Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis.	2002 Jan 22	11803030
Fifteen-year secondary leukaemia risk observed in 761 patients with Hodgkin's disease prospectively treated by MOPP or ABVD chemotherapy plus high-dose irradiation.	2002 Jul	12100147
Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer.	2002 Jul 1	12097302
[Cured from Hodgkin's disease].	2002 Jul-Aug	12206979
Topical treatment with povidone iodine reduces nitrogen mustard-induced skin collagenolytic activity.	2002 Mar	11914782
Covalent binding of nitrogen mustards to the cysteine-34 residue in human serum albumin.	2002 Mar	11914777
Involvement of phosphatidylinositol-3-kinase in membrane ruffling induced by P-glycoprotein substrates in multidrug-resistant carcinoma cells.	2002 Mar 1	11911848
European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease.	2002 Mar 15	11920535
Sulfur mustard-stimulated protease: a target for antivesicant drugs.	2002 Mar-Apr	11920939
Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection.	2002 Sep 15	12200356
Radiotherapy alone for lymphocyte-predominant Hodgkin's disease.	2002 Sep-Oct	12416895
MOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989-2000).	2002 Sep-Oct	12322709
From poison gas to wonder drug.	2002 Summer	12108457
Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas.	2003 Apr	12852367
Bilateral renal artery stenosis after abdominal radiotherapy for Hodgkin's disease.	2003 Apr	12723735
[Hodgkin's disease manifesting as paraneoplastic limbic encephalitis].	2003 Apr	12706783
The protective and therapeutic effects of zinc chloride and desferrioxamine on skin exposed to nitrogen mustard.	2003 Aug	12943035
Topical nitrogen mustard in the treatment of alopecia areata: a bilateral comparison study.	2003 Aug	12894080
Secondary myelodysplastic syndrome and acute myelogenous leukemia are significant complications following autologous stem cell transplantation for lymphoma.	2003 Aug	12858205
Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial.	2003 Feb 15	12586796
Advanced Hodgkin's disease: ABVD is better, yet is not good enough!	2003 Feb 15	12586791
Topical nitrogen mustard ointment with occlusion for Langerhans' cell histiocytosis of the scalp.	2003 Jan	12745855
[Cutaneous T-cell lymphoma following renal transplantation].	2003 Jan	12605158
Quantitative determination of the hydrolysis products of nitrogen mustards in human urine by liquid chromatography-electrospray ionization tandem mass spectrometry.	2003 Jan-Feb	12587675
Revascularization for acute coronary occlusion in a young woman following radiation.	2003 Jul	14507117
Injury induced by chemical warfare agents: characterization and treatment of ocular tissues exposed to nitrogen mustard.	2003 Jul	12824239
Analysis of treatment results in advanced Hodgkin's disease: the case for adjuvant radiotherapy.	2003 Jul 1	12788168
Radiation therapy in the treatment of Hodgkin's disease--do you see what I see?	2003 Jul 2	12837820
Myeloid clonogenic assays for comparison of the in vitro toxicity of alkylating agents.	2003 Jun	12781205
Involved-field radiotherapy for advanced Hodgkin's lymphoma.	2003 Jun 12	12802025
Early and intermediate stage Hodgkin's lymphoma--report from the Swedish National Care Programme.	2003 Mar	12605661
Synthesis and in vivo biodisposition of [14C]-quaternary ammonium-melphalan conjugate, a potential cartilage-targeted alkylating drug.	2003 Mar-Apr	12643763
Cutaneous granulomas as the first manifestation of Hodgkin's disease.	2003 May-Jun	12804995
The treatment of adults with medulloblastoma: a prospective study.	2003 Nov 1	14529781
Management of mycosis fungoides: Part 2. Treatment.	2003 Oct	14606365
[Hematologic tumors].	2003 Oct	14584273
Old wine in new bottles: reviving old therapies for alopecia areata using rodent models.	2003 Oct	14582676
[Second malignancies following Hodgkin's disease treatment in Tunisia. Retrospective study of 26 cases observed at the institute Salah-Azaïz].	2003 Oct	14522350

Patents

Sample Use Guides

In Vivo Use Guide

Intravenous Administration: the dosage of MUSTARGEN (MECHLORETHAMINE HCl ) varies with the clinical situation, the therapeutic response and the magnitude of hematologic depression. A total dose of 0.4 mg/kg of body weight for each course usually is given either as a single dose or in divided doses of 0.1 to 0.2 mg/kg per day. Intracavitary Administration: The usual dose of nitrogen mustard for intracavitary injection is 0.4 mg/kg of body weight, though 0.2 mg/kg (or 10 to 20 mg) has been used by the intrapericardial route.5,11-13 The solution is prepared, as previously described for intravenous injection, by adding 10 mL of Sterile Water for Injection or 10 mL of Sodium Chloride Injection to the vial containing 10 mg of mechlorethamine hydrochloride. (Amounts of diluent of 50 to 100 mL of normal saline have also been used.4,5) The position of the patient should be changed every 5 to 10 minutes for an hour after injection to obtain more uniform distribution of the drug throughout the serous cavity. The remaining fluid may be removed from the pleural or peritoneal cavity by paracentesis 24 to 36 hours later. The patient should be followed carefully by clinical and x-ray examination to detect reaccumulation of fluid.

Route of Administration: Other

In Vitro Use Guide

Unknown

Name

Type

Language

MECHLORETHAMINE

Common Name

English

2,2'-DICHLORO-N-METHYLDIETHYLAMINE

Common Name

English

MECHLORETHAMINE [MI]

Common Name

English

chlormethine [INN]

Common Name

English

MECHLORETHAMINE [HSDB]

Common Name

English

METHYL-.BETA.,.BETA.-DICHLORODIETHYLAMINE

Common Name

English

DIETHYLAMINE, 2,2'-DICHLORO-N-METHYL-

Systematic Name

English

NITROGEN MUSTARD (HN 2)

Common Name

English

NSC-128663

Code

English

CHLORETHAZINE

Common Name

English

CHLORMETHINE

Official Name

English

ETHANAMINE, 2-CHLORO-N-(2-CHLOROETHYL)-N-METHYL-

Systematic Name

English

NSC-757087

Code

English

NITROGEN MUSTARD

Common Name

English

MECHLORETHAMINE [VANDF]

Common Name

English

NITROGEN MUSTARD [IARC]

Common Name

English

Chlormethine [WHO-DD]

Common Name

English

NSC-10107

Code

English

Classification Tree Code System Code

LIVERTOX

NBK548509