Non-Human Toxicity Values
Oral LD50 in mice: 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.

According to an independent committee of scientific and health experts, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) may be carcinogenic. 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea is a pale yellow powder. (NTP, 1992) Semustine is an organochlorine compound, a derivative of urea, in which two hydrogen atoms on one amino group are replaced by nitrosyl and 2-chloroethyl groups, and one hydrogen atom on the other amino group is replaced by a 4-methylcyclohexyl group. It has antitumor, carcinogenic, and alkylating effects. It is an organochlorine compound belonging to the N-nitrosourea class of compounds. Semustine is a methylated derivative of carmustine and has antitumor activity. As an alkylating agent, semustine forms covalent bonds with nucleophilic centers in DNA, leading to depurination, base pair mismatches, strand breaks, and DNA-DNA crosslinking, which may potentially cause cytotoxicity. (NCI04)
A 4-methyl derivative of lomustine; (CCNU). An antitumor drug with alkylating activity.

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Therapeutic Uses
/Experimental Treatment:/Methyl-CCNU is an investigational drug used in chemotherapy to treat various cancers, including some brain cancers… It has also been used to treat lung cancer and gastrointestinal cancers.
/Experimental Treatment:/In 1988, the US National Surgical Adjuvant Breast and Intestinal Program C-01 trial reported that for patients with colon adenocarcinoma, compared with surgery alone, 1) postoperative chemotherapy using 1-(2-chloroethyl)-3-(4-trans-methylcyclohexyl)-1-nitrosourea (i.e., MeCCNU or semustine), vincristine, and 5-fluorouracil improved 5-year disease-free survival and overall survival; 2) postoperative immunotherapy using BCG improved 5-year disease-free survival and overall survival. Overall, the 5-year survival rate was higher, but the disease-free survival rate was lower. This report is a 10-year update of the trial. Between November 11, 1977, and February 28, 1983, 1166 patients with Dukes stage B and C colon adenocarcinoma who underwent resection were stratified by Dukes stage, sex, and age (<65 years or ≥65 years) and then randomly assigned to three groups: surgery alone (394 patients), adjuvant chemotherapy (379 patients), and adjuvant immunotherapy (393 patients). Patients eligible for follow-up included: 375 patients (95.2%) in the surgery alone group, 349 patients (92.1%) in the adjuvant chemotherapy group, and 372 patients (94.7%) in the adjuvant immunotherapy group. All statistical tests were two-sided. There were no significant differences in 10-year disease-free survival (hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 0.94–1.39; P = 0.17) and overall survival (HR = 1.12, 95% CI = 0.91–1.38; P = 0.27) between the chemotherapy group and the surgery-only group. Immunotherapy did not appear to prevent tumor recurrence after 10 years (relative risk [RR] = 0.99, 95% CI = 0.78–1.25; P = 0.93 between the surgery-only group and the immunotherapy group), but it was beneficial to 10-year overall survival (RR = 1.27, 95% CI = 1.03–1.56; P = 0.02 between the surgery-only group and the immunotherapy group), which was clearly due to the reduction in comorbidity-related deaths in the immunotherapy group. The disease-free survival and overall survival benefits of chemotherapy in this patient population are limited in duration, disappearing after 10 years.
Drug Warning
In clinical trials, the risk of leukemia or preleukemia following adjuvant methyl-CCNU therapy was assessed in 3633 patients with gastrointestinal cancers. Of the 2067 patients treated with methyl-CCNU, 14 cases of leukemia were reported, compared to only 1 case of acute non-lymphocytic leukemia in 1566 patients receiving other therapies (a relative risk exceeding 12-fold). Subsequent reports showed a significant dose-response relationship; after adjusting for survival time, the relative risk of nephrotoxicity in patients receiving the highest dose of methyl-CCNU was approximately 40-fold.
Dose-related nephrotoxicity following administration of certain chloroethylnitrosourea compounds (carmustine, semustine, and streptozotocin) typically manifests as elevated 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.)