DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/23570586Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22385186 | https://clinicaltrials.gov/ct2/show/NCT00335075 | https://www.ncbi.nlm.nih.gov/pubmed/21698685 | https://clinicaltrials.gov/ct2/show/NCT00427570
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23570586
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22385186 | https://clinicaltrials.gov/ct2/show/NCT00335075 | https://www.ncbi.nlm.nih.gov/pubmed/21698685 | https://clinicaltrials.gov/ct2/show/NCT00427570
Semustine is a methylated derivative of carmustine with potent 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. Semustine is primarily used to treat brain tumors, colorectal tumors, lymphomas, and stomach cancer.
CNS Activity
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21698685 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
Doses
| Dose | Population | Adverse events |
|---|---|---|
36 mg/m3 1 times / week multiple, oral Studied dose Dose: 36 mg/m3, 1 times / week Route: oral Route: multiple Dose: 36 mg/m3, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Leucopenia, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Leucopenia (25%) Sources: Thrombocytopenia (43%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Leucopenia | 25% Disc. AE |
36 mg/m3 1 times / week multiple, oral Studied dose Dose: 36 mg/m3, 1 times / week Route: oral Route: multiple Dose: 36 mg/m3, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Thrombocytopenia | 43% Disc. AE |
36 mg/m3 1 times / week multiple, oral Studied dose Dose: 36 mg/m3, 1 times / week Route: oral Route: multiple Dose: 36 mg/m3, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 3.0 |
no [IC50 9.4392 uM] | |||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
Page: 852.0 |
no | |||
Page: 581.0 |
no | |||
| yes [Inhibition 10 uM] | ||||
| yes [Inhibition 10 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 851 | 852 |
no |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011-07-14 |
|
| Interstitial chemotherapy with biodegradable BCNU (Gliadel) wafers in the treatment of malignant gliomas. | 2007-10 |
|
| Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of NSABP protocol C-01. | 2004-08-04 |
|
| 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. | 2004 |
|
| 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU). | 2002 |
|
| Anticancer drug-induced kidney disorders. | 2001-01 |
|
| Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. | 2000-05 |
|
| Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity. | 1986-11 |
|
| Comparative nephrotoxicity of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU) and chlorozotocin: functional-structural correlations in the Fischer 344 rat. | 1986-03-15 |
|
| Chemical cholecystitis after intrahepatic chemotherapy. The case for prophylactic cholecystectomy during pump placement. | 1986-03 |
|
| Enhancement by electron-affinic agents of the therapeutic effects of cytotoxic agents against the KHT tumor: structure-activity relationships. | 1982-03-01 |
|
| Chemotherapeutic effects of some alkylating derivatives of nitrosourea on the development of tumors transplacentally induced in rats by ENU. | 1976-01-31 |
|
| A phase 2 evaluation of 1-(2-chloroethyl)-3-(4- methylcyclohexyl)-1-nitrosourea (NSC 95441) in patients with advanced breast cancer. | 1974-01 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00335075
Semustine orally once every 28 days at a dose of 150 mg/m2/day.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/626984
Cell lines BE and HT (HT-29), were used for activity evaluation. BE and HT cell cultures were treated with MMeCCNU (Semustine) 50, 100, or 200 mkM. For cell culture experiments, stock drug solutions were prepared immediately before use at a concentration of 12.38 mg/ml (0.05 M) in 95% ethanol. Appropriate dilutions of the stock solution were made so that 20 mkI of drug solution were added to cultures in all experiments. Addition of 20 mkl 95% ethanol had no effect on cell growth or DNA integrity in control cells. The experiments show that line BE is sensitive to MeCCNU treatment in tissue culture, which corresponds with its response in vivo. There is a differential response to 100 mkM MeCCNU between lines BE and HT. At this dose approximately 50% of the cells in the BE cultures were lost from the plate with remaining cells showing little or no proliferation capacity, while line HT showed only a slight initial inhibition of growth with little or no cell loss
| Substance Class |
Mixture
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