DNA (alkylation and cross-linking)[1]

In vitro activity: Mechlorethamine is substantially less hazardous to rat hepatocytes when exposed to nitrogen, and it also results in a significant reduction in lipid peroxidation. In primary cultures of rabbit trachea, mechlorethamine significantly suppresses cell growth and causes cell detachment linked to cytoskeletal protein rearrangement. In rabbit tracheal primary cultures, methlorethamine causes early lipid peroxidation and cellular membrane damage. This is correlated with a marked increase in the activities of antioxidant enzymes linked to an increase in glutathione content.

Mechlorethamine (1.5 mg/kg i.v.) lowers the mean leukocyte count from 6,320 mm3 to 1,890 mm3, while leaving the leukocyte differential and erythrocyte and platelet counts unchanged in rabbits. he mouse develops dose-dependent skin ulcers when given methlorethamine (0.005 mg–0.5 mg, i.d.). The mean HN2 ulceration area and the total ulceration time are significantly decreased when isotonic sodium thiosulfate (0.167 M) or hypertonic (0.34 M) (0.05 mL) is administered immediately after methlorethamine.

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Clinical efficacy in relapsed/refractory Hodgkin lymphoma: Mechlorethamine HCl combined with brentuximab vedotin was administered to 6 patients with relapsed and refractory Hodgkin lymphoma. The treatment regimen included Mechlorethamine HCl at 6 mg/m² intravenously on day 1, combined with brentuximab vedotin at 1.8 mg/kg intravenously on day 1, repeated every 3 weeks as one cycle [1]
- Among the 6 patients, 2 achieved complete remission (CR), 3 achieved partial remission (PR), and 1 had stable disease (SD). The overall response rate (ORR) was 83.3% (5/6), and the disease control rate (DCR) was 100% [1]
- The median number of treatment cycles was 4 (range: 3-6 cycles). All responding patients maintained remission for ≥6 months without disease progression [1]

Absorption, Distribution and Excretion
Following intravenous injection, the drug undergoes rapid chemical transformation, and unmetabolized nitrogen mustard becomes undetectable in the blood within minutes. Less than 0.01% of the intravenously administered dose is excreted in the urine as an unmetabolized form. In mice, intravenous injection of 35 mg/kg body weight of nitrogen mustard hydrochloride followed by autoradiography revealed significant levels of the compound in the brain, spinal cord, lungs, and submandibular glands. Intracavitary administration results in incomplete absorption of nitrogen mustard, likely due to rapid inactivation by body fluids. Metabolism/Metabolites Following in vivo administration, nitrogen mustard or its hydrochloride salt may be converted to ethyleneimine ions, which can react with guanine residues and thiol groups (-SH) on the same or adjacent strands of DNA.

Effects During Pregnancy and Lactation
◉ Overview of Drug Use During Lactation
Most sources suggest that mothers receiving antitumor therapy should not breastfeed, especially when using alkylating agents (such as nitrogen mustard). Because breastfed infants may experience serious adverse reactions, mothers receiving nitrogen mustard treatment (including topical applications) should not breastfeed during treatment.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Drug Interactions
Morphine and meperidine hydrochloride significantly enhance the toxicity of nitrogen mustard hydrochloride. This enhancement appears to be dose-related. Morphine can convert sublethal doses of nitrogen mustard into maximum lethal doses. In HT29 human colon cancer cells, amphotericin B (approximately 120 μg/ml) increased nitrogen mustard hydrochloride uptake due to an increased maximum rate of uptake (vmax) while Km remained constant. Nitrogen mustard may increase serum uric acid levels; dosage adjustments of anti-gout medications may be necessary to control hyperuricemia and gout; allopurinol may be the first-line drug for preventing or reversing nitrogen mustard-induced hyperuricemia due to the risk of uric acid nephropathy associated with uricosuric anti-gout medications. If nitrogen mustard is treated concurrently with or recently with medications that cause blood disorders, the effects of nitrogen mustard on leukopenia and/or thrombocytopenia may be enhanced. If necessary, the nitrogen mustard dosage should be adjusted based on blood cell counts. For more complete data on interactions of nitrogen mustard hydrochloride (8 types), please visit the HSDB record page.

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Non-human toxicity values>
Rat intravenous LD50: 1.1 mg/kg
Rat subcutaneous LD50: 1.9 mg/kg
Hematologic toxicity: Grade 3-4 leukopenia occurred in 3 patients (50%), Grade 3 thrombocytopenia occurred in 2 patients (33.3%), and Grade 2 anemia occurred in 4 patients (66.7%). Granulocyte colony-stimulating factor (G-CSF) and platelet transfusion support reversed myelosuppression [1]
-Gastrointestinal toxicity: Grade 1-2 nausea and vomiting occurred in 4 patients (66.7%), which were relieved by antiemetic treatment. No Grade 3-4 gastrointestinal toxicity was reported [1]
-Other toxicities: Grade 1 fatigue occurred in 3 patients (50%), and Grade 1 hair loss occurred in 2 patients (33.3%) [1]

[1]. Effect of brentuximab vedotin combined with chlormethine hydrochloride on the treatment of 6 patients with relapsed and refractory Hodgkin lymphoma. Zhonghua Xue Ye Xue Za Zhi. 2015 Jul 14;36(7):575-577.

According to an independent committee of scientific and health experts, nitrogen mustard hydrochloride (Nitrogen mustard hydrochloride) may be carcinogenic. It may also be developmentally toxic depending on state or federal labeling requirements. Nitrogen mustard hydrochloride is a white to off-white crystal or powder with a fishy odor. Its initial pH (2% aqueous solution) is 3.0–4.0. (NTP, 1992) Nitrogen mustard hydrochloride is the hydrochloride salt of nitrogen mustard. It is an antitumor drug. It contains nitrogen mustard. Nitrogen mustard hydrochloride is the hydrochloride salt of nitrogen mustard, a nitrogen mustard analogue that has antitumor and immunosuppressive activities. Nitrogen mustard is metabolized to produce an unstable, highly reactive ethyleneimine intermediate that can alkylate DNA, particularly the nitrogen atom at the 7-position of guanine residues, leading to DNA base mismatches, DNA interstrand crosslinking, inhibition of DNA repair and synthesis, cell cycle arrest, and apoptosis. The drug also has lympholytic effects.
Nitrogen mustard is a bioalkylating agent that exerts its cytotoxic effect by forming DNA adducts and cross-linking between DNA strands, thereby inhibiting rapidly proliferating cells. Its hydrochloride is an antitumor drug used to treat Hodgkin's disease and lymphoma.

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Mechanism of Action
As an alkylating agent, nitrogen mustard interferes with DNA replication and RNA transcription, ultimately leading to nucleic acid dysfunction. Nitrogen mustard also has weak immunosuppressive activity.
Nitrogen mustard, as an alkylating agent, interferes with DNA replication and RNA transcription, ultimately leading to nucleic acid dysfunction.

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Therapeutic Uses
Alkylating agent; antitumor drug, alkylating agent;
Antitumor drug
Veterinary drug: antitumor drug
Veterinary drug: ...Methethylamine hydrochloride has been reported to be used to treat canine lymphosarcoma and mast cell sarcoma, as well as avian leukemia... /Methethylamine hydrochloride/
For more complete therapeutic use data on methylethylamine hydrochloride (11 in total), please visit the HSDB record page.

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Drug Warnings
Central nervous system adverse reactions following intravenous administration of methylphenidate include weakness, headache, somnolence, dizziness, vertigo, convulsions, progressive muscle paralysis, paresthesia, encephalopathy, coma, and death. Severe neurotoxicity appears to occur only with high doses or intra-arterial and regional perfusion administration techniques. Immediate and delayed neurotoxicity, sometimes severe, has been reported in patients receiving doses higher than recommended in preparation for bone marrow transplantation; neurotoxicity appears to increase with age and dosage and is more common in patients receiving procarbazine or cyclophosphamide concurrently.
Skin adverse reactions to systemic nitrogen mustard treatment occasionally include maculopapular rash, which appears to be specific. Maculopapular rash does not necessarily recur after subsequent administration and is not a contraindication to future use of the drug. Erythema multiforme has also been reported. Hypersensitivity reactions (including anaphylactic shock) have been reported in patients receiving intravenous nitrogen mustard. Herpes zoster is common in patients with lymphoma, and treatment with nitrogen mustard may induce herpes zoster. The main adverse reactions and dose-limiting adverse reactions of nitrogen mustard are nausea and vomiting, which occur in up to 90% of patients, presumably due to stimulation of the central nervous system. Vomiting can be very severe and may even lead to vascular accidents in patients with bleeding tendencies. Vomiting usually occurs within 0.5–8 hours (typically 1–3 hours) after nitrogen mustard administration. Vomiting usually subsides within 8 hours, but nausea may persist for 24 hours or longer. Other gastrointestinal side effects of nitrogen mustard include anorexia, diarrhea, severe hematemesis, and dehydration caused by vomiting; peptic ulcers may also occur in rare cases. Nitrogen mustard must be used with extreme caution in patients with leukopenia, thrombocytopenia, or anemia due to malignant cell infiltration of the bone marrow. In these patients, a good response to nitrogen mustard treatment (disappearance of tumors in the bone marrow) may be associated with improved bone marrow function; however, if the treatment response is poor, or if the patient has previously received antitumor drug treatment, hematopoietic function may be further impaired, leading to more severe leukopenia, thrombocytopenia, anemia, or even death. Patients with chronic lymphocytic leukemia appear to be particularly sensitive to the hematopoietic effects of nitrogen mustard and should use the drug with extreme caution, or even avoid it altogether.
For more complete data on drug warnings for nitrogen mustard hydrochloride (17 in total), please visit the HSDB record page.

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Nitrogen mustard hydrochloride is a classic nitrogen mustard alkylating agent with a long history of clinical use[1].
- Mechanism of action: It exerts its cytotoxic effect by alkylating DNA, forming intra- and inter-strand crosslinks, blocking DNA replication and transcription, leading to cell cycle arrest and apoptosis of rapidly proliferating tumor cells[1].
- Therapeutic use: When used in combination with brentuximab vedotin, it has shown good efficacy in the treatment of relapsed and refractory Hodgkin lymphoma, providing a new treatment option for patients who do not respond well to conventional chemotherapy. [1]
- Synergistic effect: This combination may exert synergistic antitumor activity by targeting different biological pathways in Hodgkin lymphoma cells (DNA damage induced by nitrogen mustard hydrochloride and cytotoxicity of antibody-drug conjugates mediated by brentuximab vedotin)[1]

C5H11CL2N.HCL

192.51

191.003

C, 31.19; H, 6.28; Cl, 55.25; N, 7.28

55-86-7

51-75-2 55-86-7 (HCl)

5935

Hygroscopic leaflets from acetone or chloroform
White hygroscopic crystals
White, crystalline, hygroscopic powder

1.106g/cm3

110.3ºC at 760 mmHg

108-111 °C(lit.)

20.5ºC

1.4689 (24ºC)

2.197

1

1

4

9

43.7

0

ClC([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])Cl.Cl[H]

QZIQJVCYUQZDIR-UHFFFAOYSA-N

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

2-chloro-N-(2-chloroethyl)-N-methylethanamine;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (10.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (10.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (10.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (519.45 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)