Non-Human Toxicity Values
LD50 Mouse oral 49,900 ug/kg

[1]. Molecular modeling and spectroscopic studies of semustine binding with DNA and its comparison with lomustine-DNA adduct formation. J Biomol Struct Dyn. 2015;33(8):1653-68.

1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Methyl-CCNU) can cause cancer according to an independent committee of scientific and health experts.
1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea is a light yellow powder. (NTP, 1992)
Semustine is an organochlorine compound that is urea in which the two hydrogens on one of the amino groups are replaced by nitroso and 2-chloroethyl groups and one hydrogen from the other amino group is replaced by a 4-methylcyclohexyl group. It has a role as an antineoplastic agent, a carcinogenic agent and an alkylating agent. It is an organochlorine compound and a member of N-nitrosoureas.
Semustine is a methylated derivative of carmustine with antineoplastic activity. As an alkylating agent, semustine forms covalent linkages with nucleophilic centers in DNA, causing depurination, base-pair miscoding, strand scission, and DNA-DNA cross-linking, which may result in cytotoxicity. (NCI04)
4-Methyl derivative of LOMUSTINE; (CCNU). An antineoplastic agent which functions as an alkylating agent.

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Therapeutic Uses
/EXPERIMENTAL THERAPY:/ Methyl-CCNU is an investigational drug used in chemotherapy to treat several types of cancers, including some brain cancers ... It also has been used to treat cancers of the lung and digestive tract.
/EXPERIMENTAL THERAPY/ The National Surgical Adjuvant Breast and Bowel Project C-01 trial reported in 1988 that, for patients with adenocarcinoma of the colon, compared with surgery alone, 1) postoperative chemotherapy with 1-(2-chloroethyl)-3-(4-trans-methylcyclohexyl)-1-nitrosourea (i.e., MeCCNU or semustine), vincristine, and 5-fluorouracil was associated with better 5-year disease-free and overall survival and 2) postoperative immunotherapy with bacillus Calmette-Guerin was associated with better 5-year overall, but not disease-free, survival. /This report is/ a 10-year update of this trial. Between November 11, 1977, and February 28, 1983, 1166 patients with resected Dukes' stage B and C adenocarcinoma of the colon were stratified by Dukes' stage, sex, and age (<65 years or > or =65 years) and then randomly assigned to receive no further treatment (surgery alone; 394 patients), adjuvant chemotherapy (379 patients), or adjuvant immunotherapy (393 patients). Those eligible for follow-up included 375 (95.2%) patients in the surgery-alone group, 349 (92.1%) patients in the adjuvant-chemotherapy group, and 372 (94.7%) patients in the adjuvant-immunotherapy group. All statistical tests were two-sided. No difference was observed between patients in the chemotherapy group and those in the surgery-alone group in 10-year disease-free survival (hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 0.94 to 1.39; P =.17) or overall survival (HR = 1.12, 95% CI = 0.91 to 1.38; P=.27). Immunotherapy did not appear to prevent tumor relapse after 10 years (for surgery alone versus immunotherapy, relative risk [RR] = 0.99, 95% CI = 0.78 to 1.25; P =.93) but had a beneficial effect on 10-year overall survival (for surgery alone versus immunotherapy, RR = 1.27, 95% CI = 1.03 to 1.56; P =.02) that apparently results from a reduction in deaths associated with comorbidities in the immunotherapy group. The disease-free and overall survival benefit associated with chemotherapy in this patient population is of limited duration, disappearing after 10 years.

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Drug Warnings
The risk of developing leukemia or preleukemia following adjuvant treatment with methyl- CCNU during clinical trials was evaluated in 3,633 patients with gastrointestinal cancer. Fourteen cases of leukemic disorders were reported out of 2,067 patients given methyl-CCNU compared to only one case of acute nonlymphocytic leukemia out of 1,566 patients given other therapies (relative risk of over 12 fold). A strong dose-response relationship was shown in a later report; a relative risk of about 40 fold, adjusted for survival time, was found for patients treated with the highest dose of methyl-CCNU.
Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uremia and proteinuria .....

C10H18N3O2CL

247.72182

247.109

13909-09-6

5198

Light yellow to yellow solid powder

1.31 g/cm3

64°C (rough estimate)

1.51

2.887

1

3

3

16

242

0

FVLVBPDQNARYJU-UHFFFAOYSA-N

InChI=1S/C10H18ClN3O2/c1-8-2-4-9(5-3-8)12-10(15)14(13-16)7-6-11/h8-9H,2-7H2,1H3,(H,12,15)

1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product is not stable in solution, please use freshly prepared working solution for optimal results.

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

DMSO : ~100 mg/mL (~403.68 mM)
Ethanol : ~50 mg/mL (~201.84 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.09 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 25.0 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: ≥ 2.5 mg/mL (10.09 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 25.0 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: ≥ 2.5 mg/mL (10.09 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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