MECHLORETHAMINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C5H11Cl2N.ClH
Molecular Weight	192.514
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of MECHLORETHAMINE HYDROCHLORIDE

Structure Search

SMILES

Cl.CN(CCCl)CCCl

InChI

InChIKey=QZIQJVCYUQZDIR-UHFFFAOYSA-N

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

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 282 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19480393	Crosslinking Agent 83

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 8583	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 1949
Lymphosarcoma 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8583	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 1949
Chronic lymphocytic leukemia 59 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8583	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 1949
Chronic myelocytic leukemia 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8583	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 1949
Mycosis fungoides 31 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8583	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 1949

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	unhealthy, 14-80 Health Status: unhealthy Age Group: 14-80 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4569376	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
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	unhealthy, 32-81 Health Status: unhealthy Age Group: 32-81 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4569376	Disc. AE: Pancytopenia... AEs leading to discontinuation/dose reduction: Pancytopenia (5.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/4569376
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	unhealthy, 44 Health Status: unhealthy Age Group: 44 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/2933055	Disc. AE: Contact dermatitis... AEs leading to discontinuation/dose reduction: Contact dermatitis (75%) Sources: https://pubmed.ncbi.nlm.nih.gov/2933055
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf	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
0.4 mg/kg single, intravenous 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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Disc. AE: Amyloidosis... AEs leading to discontinuation/dose reduction: Amyloidosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf

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	unhealthy, 14-80 Health Status: unhealthy Age Group: 14-80 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4569376
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	unhealthy, 14-80 Health Status: unhealthy Age Group: 14-80 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4569376
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	unhealthy, 32-81 Health Status: unhealthy Age Group: 32-81 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4569376
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	unhealthy, 44 Health Status: unhealthy Age Group: 44 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/2933055
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf
Amyloidosis	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://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf

Sourcing

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

PubMed

Title	Date	PubMed
The treatment of adults with medulloblastoma: a prospective study.	2003-11-01	14529781
Management of mycosis fungoides: Part 2. Treatment.	2003-10	14606365
[Hematologic tumors].	2003-10	14584273
Old wine in new bottles: reviving old therapies for alopecia areata using rodent models.	2003-10	14582676
[Second malignancies following Hodgkin's disease treatment in Tunisia. Retrospective study of 26 cases observed at the institute Salah-Azaïz].	2003-10	14522350
Alleviation of mutagenic effects of polycyclic aromatic agents (quinacrine mustard, ICR-191 and ICR-170) by caffeine and pentoxifylline.	2003-09-29	14563530
Radiotherapy for advanced Hodgkin's disease.	2003-09-18	13679537
The protective and therapeutic effects of zinc chloride and desferrioxamine on skin exposed to nitrogen mustard.	2003-08	12943035
Topical nitrogen mustard in the treatment of alopecia areata: a bilateral comparison study.	2003-08	12894080
Secondary myelodysplastic syndrome and acute myelogenous leukemia are significant complications following autologous stem cell transplantation for lymphoma.	2003-08	12858205
Radiation therapy in the treatment of Hodgkin's disease--do you see what I see?	2003-07-02	12837820
Analysis of treatment results in advanced Hodgkin's disease: the case for adjuvant radiotherapy.	2003-07-01	12788168
Revascularization for acute coronary occlusion in a young woman following radiation.	2003-07	14507117
Injury induced by chemical warfare agents: characterization and treatment of ocular tissues exposed to nitrogen mustard.	2003-07	12824239
High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy.	2003-06-15	12805333
Cutaneous granulomas as the first manifestation of Hodgkin's disease.	2003-06-14	12804995
Involved-field radiotherapy for advanced Hodgkin's lymphoma.	2003-06-12	12802025
Myeloid clonogenic assays for comparison of the in vitro toxicity of alkylating agents.	2003-06	12781205
Impaired healing of nitrogen mustard wounds in CXCR2 null mice.	2003-05-20	12753603
Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas.	2003-04	12852367
Bilateral renal artery stenosis after abdominal radiotherapy for Hodgkin's disease.	2003-04	12723735
Differential diagnosis of Fanconi anemia by nitrogen mustard and diepoxybutane.	2003-04	12707724
[Hodgkin's disease manifesting as paraneoplastic limbic encephalitis].	2003-04	12706783
Synthesis and in vivo biodisposition of [14C]-quaternary ammonium-melphalan conjugate, a potential cartilage-targeted alkylating drug.	2003-03-20	12643763
Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study.	2003-03-01	12393427
Early and intermediate stage Hodgkin's lymphoma--report from the Swedish National Care Programme.	2003-03	12605661
Topical mechlorethamine restores autoimmune-arrested follicular activity in mice with an alopecia areata-like disease by targeting infiltrated lymphocytes.	2003-03	12603852
Quantitative determination of the hydrolysis products of nitrogen mustards in human urine by liquid chromatography-electrospray ionization tandem mass spectrometry.	2003-02-18	12587675
Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial.	2003-02-15	12586796
Advanced Hodgkin's disease: ABVD is better, yet is not good enough!	2003-02-15	12586791
Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience.	2003-02	12588222
Improved survival in HIV-related Hodgkin's lymphoma since the introduction of highly active antiretroviral therapy.	2003-01-03	12478072
Topical nitrogen mustard ointment with occlusion for Langerhans' cell histiocytosis of the scalp.	2003-01	12745855
[Cutaneous T-cell lymphoma following renal transplantation].	2003-01	12605158
An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.	2002-12-15	12467067
[Psoriasis of the scalp].	2002-12	12536184
Postpneumonectomy-like syndrome after chemoradiation therapy for lymphoma.	2002-12	12453864
Serum levels of soluble CD30 improve International Prognostic Score in predicting the outcome of advanced Hodgkin's lymphoma.	2002-12	12453859
Pathways of reductive fragmentation of heterocyclic nitroarylmethyl quaternary ammonium prodrugs of mechlorethamine.	2002-12	12452778
Radiotherapy alone for lymphocyte-predominant Hodgkin's disease.	2002-11-06	12416895
Evaluation of a 1-h exposure time to mechlorethamine in patients undergoing topical treatment.	2002-11	12410702
Long-term results of conventional-dose salvage chemotherapy in patients with refractory and relapsed Hodgkin's disease (Croatian experience).	2002-10	12377656
MOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989-2000).	2002-09-27	12322709
Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection.	2002-09-15	12200356
[Cured from Hodgkin's disease].	2002-09-06	12206979
The ability to engage enterocyte apoptosis does not predict long-term crypt survival in p53 and Msh2 deficient mice.	2002-08-29	12185594
[Advanced oxidation protein products in pregnancy].	2002-07	12373919
[Z-form of intraphage DNA].	2002	12534267
From poison gas to wonder drug.	2002	12108457
A pilot study on the influence of a corticotropin (4-9) analogue on Vinca alkaloid-induced neuropathy.	1992-10	1329697

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 HYDROCHLORIDE

Common Name

English

CHLORMETHINE HYDROCHLORIDE

Preferred Name

English

VALCHLOR

Brand Name

English

MECHLORETHAMINE HYDROCHLORIDE [VANDF]

Common Name

English

MECHLORETHAMINE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

MECHLORETHAMINE HCL

Common Name

English

CHLORMETHINE HYDROCHLORIDE [MART.]

Common Name

English

CHLORMETHINE HYDROCHLORIDE [WHO-IP]

Common Name

English

2,2'-DICHLORO-N-METHYLDIETHYLAMINE HYDROCHLORIDE

Common Name

English

MECHLORETHAMINE HYDROCHLORIDE [MI]

Common Name

English

MUSTARGEN

Brand Name

English

MECHLORETHAMINE HYDROCHLORIDE [USP-RS]

Common Name

English

NSC-762

Code

English

MECHLORETHAMINE HYDROCHLORIDE [HSDB]

Common Name

English

CHLORMETHINE HCL

Common Name

English

MECHLORETHAMINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

CHLORMETHINI HYDROCHLORIDUM [WHO-IP LATIN]

Common Name

English

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

Systematic Name

English

Chlormethine hydrochloride [WHO-DD]

Common Name

English

2-CHLORO-N-(2-CHLOROETHYL)-N-METHYLETHANAMINE HYDROCHLORIDE

Systematic Name

English

MUSTINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C697