Synonym
chloramin; chlorethamine HCl; chlorethamine hydrochloride
IUPAC/Chemical Name
2-chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride
InChi Key
QZIQJVCYUQZDIR-UHFFFAOYSA-N
InChi Code
InChI=1S/C5H11Cl2N.ClH/c1-8(4-2-6)5-3-7;/h2-5H2,1H3;1H
SMILES Code
ClCCN(CCCl)C.[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
mechlorethamine hydrochloride is the hydrochloride salt of mechlorethamine, a nitrogen mustard and an analogue of sulfur mustard, with antineoplastic and immunosuppressive activities. Mechlorethamine is metabolized to an unstable, highly reactive ethyleniminium intemediate that alkylates DNA, particularly the 7 nitrogen of guanine residues, resulting in DNA base pair mismatching, DNA interstrand crosslinking, the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis. This agent also exhibits lympholytic properties. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)
History
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 chemical warfare research, in particular a 1943 accident in Bari, Italy which exposed civilians and soldiers-- it was noted that white cell counts of exposed patients decreased, suggesting a possible therapy for the cancer Hodgkin's lymphoma.
DRUG DESCRIPTION
MUSTARGEN, an antineoplastic nitrogen mustard also known as HN2 hydrochloride, is a nitrogen analog of sulfur mustard. It is a light yellow brown, crystalline, hygroscopic powder that is very soluble in water and also soluble in alcohol. Mechlorethamine hydrochloride is designated chemically as 2-chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride. The molecular weight is 192.52 and the melting point is 108-111°C. The empirical formula is C5H11Cl2N•HCl, and the structural formula is: CH3N(CH2CH2Cl)2•HCl. Trituration of MUSTARGEN is a sterile, light yellow brown crystalline powder for injection by the intravenous or intracavitary routes after dissolution. Each vial of MUSTARGEN contains 10 mg of mechlorethamine hydrochloride triturated with sodium chloride q.s. 100 mg. When dissolved with 10 mL Sterile Water for Injection or 0.9% Sodium Chloride Injection, the resulting solution has a pH of 3-5 at a concentration of 1 mg mechlorethamine HCl per mL.
Biological target:
Chlormethine hydrochloride is a vesicant and necrotizing irritant destructive to mucous membranes.
In vitro activity:
The aim of this in vitro study was to characterize the early effects of short-term exposure to low concentrations of mechlorethamine (HN2), a nitrogen mustard, on rabbit tracheal primary cultures. Marked inhibition of cell growth was observed without recovery until 14 days after the treatment with sublethal doses of HN2.
Reference: Toxicol In Vitro. 1997 Oct;11(5):695-702. https://pubmed.ncbi.nlm.nih.gov/20654373/
In vivo activity:
Mouse skin toxicity studies were carried out to find a local antidote to decrease the severity of tissue damage by this agent. Intradermal (i.d.) HN2 (0.005-0.5 mg) caused dose-dependent skin ulcers in the mouse. Isotonic sodium thiosulfate Na2S2O3 (0.167 M) or hypertonic (0.34 M) Na2S2O3 (0.05 ml) given immediately after HN2 significantly reduced the mean HN2 ulceration area and the total time of ulceration.
Reference: Cancer Chemother Pharmacol. 1988;22(4):299-302. https://pubmed.ncbi.nlm.nih.gov/3168143/
|
Solvent |
mg/mL |
mM |
| Solubility |
| Ethanol |
39.0 |
202.59 |
| Water |
69.5 |
361.02 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
192.51
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Giuliani I, Baeza-Squiban A, Marano F. Early cytotoxic effects of mechlorethamine, a nitrogen mustard, on mammalian airway epithelium. Toxicol In Vitro. 1997 Oct;11(5):695-702. doi: 10.1016/s0887-2333(97)00070-2. PMID: 20654373.
2. Khan S, Ramwani JJ, O'Brien PJ. Hepatocyte toxicity of mechlorethamine and other alkylating anticancer drugs. Role of lipid peroxidation. Biochem Pharmacol. 1992 May 8;43(9):1963-7. doi: 10.1016/0006-2952(92)90639-z. PMID: 1596284.
3. Rao TJR, Mao G, Cuffari BJ, Billack B. Dysregulation of the mTOR pathway by mechlorethamine. Toxicology. 2023 Jan 26;486:153434. doi: 10.1016/j.tox.2023.153434. Epub ahead of print. PMID: 36708981.
4. Dorr RT, Soble M, Alberts DS. Efficacy of sodium thiosulfate as a local antidote to mechlorethamine skin toxicity in the mouse. Cancer Chemother Pharmacol. 1988;22(4):299-302. doi: 10.1007/BF00254235. PMID: 3168143.
In vitro protocol:
1. Giuliani I, Baeza-Squiban A, Marano F. Early cytotoxic effects of mechlorethamine, a nitrogen mustard, on mammalian airway epithelium. Toxicol In Vitro. 1997 Oct;11(5):695-702. doi: 10.1016/s0887-2333(97)00070-2. PMID: 20654373.
2. Khan S, Ramwani JJ, O'Brien PJ. Hepatocyte toxicity of mechlorethamine and other alkylating anticancer drugs. Role of lipid peroxidation. Biochem Pharmacol. 1992 May 8;43(9):1963-7. doi: 10.1016/0006-2952(92)90639-z. PMID: 1596284.
In vivo protocol:
1. Rao TJR, Mao G, Cuffari BJ, Billack B. Dysregulation of the mTOR pathway by mechlorethamine. Toxicology. 2023 Jan 26;486:153434. doi: 10.1016/j.tox.2023.153434. Epub ahead of print. PMID: 36708981.
2. Dorr RT, Soble M, Alberts DS. Efficacy of sodium thiosulfate as a local antidote to mechlorethamine skin toxicity in the mouse. Cancer Chemother Pharmacol. 1988;22(4):299-302. doi: 10.1007/BF00254235. PMID: 3168143.
1: Sharma M, Vijayaraghavan R, Gautam A. DRDE-07 and its analogues as promising cytoprotectants to nitrogen mustard (HN-2)--an alkylating anticancer and chemical warfare agent. Toxicol Lett. 2009 Aug 10;188(3):243-50. Epub 2009 May 3. PubMed PMID: 19397960.
2: Armand JP, Ribrag V, Harrousseau JL, Abrey L. Reappraisal of the use of procarbazine in the treatment of lymphomas and brain tumors. Ther Clin Risk Manag. 2007 Jun;3(2):213-24. PubMed PMID: 18360630; PubMed Central PMCID: PMC1936303.
3: Bartzatt R. Alkylation activity and molecular properties of two antineoplastic agents that utilise indometacin and a conjugate of aspirin with 2-aminonicotinic acid to transport nitrogen mustard groups. Drugs R D. 2007;8(6):363-72. PubMed PMID: 17963427.
4: Zhang X, Ling MT, Wong YC, Wang X. Evidence of a novel antiapoptotic factor: role of inhibitor of differentiation or DNA binding (Id-1) in anticancer drug-induced apoptosis. Cancer Sci. 2007 Mar;98(3):308-14. PubMed PMID: 17214747.
5: He D, Zhang D, Wei G, Lin T, Li X. Cytoskeleton vimentin disruption of mouse sertoli cells injured by nitrogen mustard in vitro. J Androl. 2007 May-Jun;28(3):389-96. Epub 2006 Dec 27. PubMed PMID: 17192600.
6: Dutta S, Abe H, Aoyagi S, Kibayashi C, Gates KS. DNA damage by fasicularin. J Am Chem Soc. 2005 Nov 2;127(43):15004-5. PubMed PMID: 16248621.
7: Eklund JW, Trifilio S, Mulcahy MF. Chemotherapy dosing in the setting of liver dysfunction. Oncology (Williston Park). 2005 Jul;19(8):1057-63; discussion 1063-4, 1069. Review. PubMed PMID: 16131047.
8: Guo CC, Tong RB, Li KL. Chloroalkyl piperazine and nitrogen mustard porphyrins: synthesis and anticancer activity. Bioorg Med Chem. 2004 May 1;12(9):2469-75. PubMed PMID: 15080942.
9: Rapp M, Giraud I, Maurizis JC, Galmier MJ, Madelmont JC. Synthesis and in vivo biodisposition of [14C]-quaternary ammonium-melphalan conjugate, a potential cartilage-targeted alkylating drug. Bioconjug Chem. 2003 Mar-Apr;14(2):500-6. PubMed PMID: 12643763.
10: Kapuscinski J, Ardelt B, Piosik J, Zdunek M, Darzynkiewicz Z. The modulation of the DNA-damaging effect of polycyclic aromatic agents by xanthines. Part I. Reduction of cytostatic effects of quinacrine mustard by caffeine. Biochem Pharmacol. 2002 Feb 15;63(4):625-34. PubMed PMID: 11992630.
