Lomustine
Lomustin · cinu · CCNU · ceenu · rb1509 · cecenu · sri2200 · nsc79037

Identifiers & Physical Properties
| CAS No. | 13010-47-4 |
|---|---|
| Molecular formula | C9H16ClN3O2 |
| Average molar mass | 233.69 g/mol |
| Monoisotopic mass | 233.0931045 g/mol |
| SMILES | O=NN(CCCl)C(=O)NC1CCCCC1 |
| InChIKey | GQYIWUVLTXOXAJ-UHFFFAOYSA-N |
| PubChem CID | 3950 |
| ChEMBL | CHEMBL2062293 |
| ChEBI | CHEBI:6520 |
| EC No. | 235-859-2 |
| DTXSID | DTXSID2023222 |
Chemical & Physical Properties
| XLogP | 2.8 |
|---|---|
| Topological polar surface area | 61.8 |
| Hydrogen bond donors | 1 |
| Hydrogen bond acceptors | 3 |
| Rotatable bonds | 3 |
| Heavy atoms | 15 |
| Formal charge | 0 |
| Complexity | 219 |
| Drugs | Pharmaceuticals -> Listed in ZINC15 |
| SpringerMaterials Properties | 15N nuclear magnetic resonance spectrum |
| LogP (partition coefficient) | log Kow = 2.83 |
| Color/Form | SolidYellow powder |
| Solubility | Soluble in ethanolFreely soluble in chloroformsoluble in acetone.Solubility in water, 0.1N NaOH, 0.1N HCl, or 10% ethanol: <0.05 mg/mLin absolute ethanol: 70 mg/mL7.55e-01 g/LPractically insoluble in water, freely soluble in acetone and in methylene chloride, soluble in ethanol (96 per cent). |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Decomposition | Hazardous decomposition products formed under fire conditions: Carbon oxides, nitrogen oxides (NOx), hydrogen chloride gas. |
| Melting point | 88-90 °C88 - 90 °C |
| Physical Description | Solid |
| Boiling point | 63.6°C (rough estimate) |
| Density | 1.3840 (rough estimate) |
| Refractive index | 1.5790 (estimate) |
| Storage conditions | 2-8°C |
| pKa (acidity coefficient) | 10.88±0.20(Predicted) |
| Physical state | Solid |
| Color | Light orange to Yellow to Green |
| Merck | 14,5564 |
| Henry's law constant | 5.5×104 mol/(m3Pa) at 25℃, HSDB (2015) |
| InChI | InChI=1S/C9H16ClN3O2/c10-6-7-13(12-15)9(14)11-8-4-2-1-3-5-8/h8H,1-7H2,(H,11,14) |
| InChIKey | GQYIWUVLTXOXAJ-UHFFFAOYSA-N |
| SMILES | N(CCCl)(N=O)C(NC1CCCCC1)=O |
| CAS DataBase Reference | 13010-47-4(CAS DataBase Reference) |
| NCI Dictionary of Cancer Terms | CCNUlomustine |
| FDA UNII | 7BRF0Z81KG |
| NCI Drug Dictionary | lomustine |
| ATC code | L01AD02 |
| IARC | 2A (Vol. 26, Sup 7) 1987 |
| EPA Substance Registry System | 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (13010-47-4) |
| UNSPSC Code | 41116107 |
| NACRES | NA.25 |
| Protein binding | 60% |
| Excreted unchanged in urine | 50 (as metabolites) |
| Biological half-life | 16-48 (metabolites) |
| GHS pictogram | GHS06,GHS08 |
| Signal word | Danger |
| GHS hazard statements | H301-H350 |
| GHS precautionary statements | P201-P280-P301+P330+P331+P310-P308+P313 |
| Personal protective equipment (PPE) | Eyeshields, Faceshields, Gloves, type P3 (EN 143) respirator cartridges |
| Hazard symbols | T |
| Risk statements (R) | 45-25 |
| Safety statements (S) | 53-45 |
| UN transport number | 3249 |
| Water hazard class (WGK) | 3 |
| RTECS number | YS4900000 |
| Hazard class | 6.1(a)Acute Tox. 3 OralCarc. 1B |
| Packing group | II |
| Customs code | 29299090 |
| Storage class | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| Hazardous substances data | 13010-47-4(Hazardous Substances Data) |
| Toxicity | LD50 in male mice (mg/kg): 51 orally56 i.p.61 s.c. (Thompson, Larson) |
Safety & Regulations
| GHS classification | DangerH228 (34.4%): Flammable solid [Danger Flammable solids]P203, P210, P234, P235, P240, P241, P260, P264, P270, P280, P301+P316, P308+P316, P318, P319, P321, P330, P370+P378, P403, P405, P410, P411, P420, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 64 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H301: Toxic if swallowed [Danger Acute toxicity, oral] |
|---|---|
| Regulatory information | Hazard Traits - CarcinogenicityDevelopmental Toxicity |
| Other safety information | IMAP assessments - Urea, N-(2-chloroethyl)-N'-cyclohexyl-N-nitroso-: Environment tier I assessment |
| FDA requirements | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl lomustine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Special Reports | National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (13010-47-4) is listed as reasonably anticipated to be a human carcinogen. First listed in the Fourth Annual Report on Carcinogens (1985) as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s035ccnu.pdf] |
| Toxic Combustion Products | Hazardous decomposition products formed under fire conditions: Carbon oxides, nitrogen oxides (NOx), hydrogen chloride gas. |
| Hazard Classes and Categories | Flam. Sol. 1 (34.4%)Acute toxicity (Oral) - Category 3 |
| Shipment Methods and Regulations | /PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/ |
Applications & Uses
Description
Lomustine is a pale yellow powder. Molecularweight = 233.73; Freezing/Melting point = 90℃. Insolublein water.
Uses
Chloroethylnitrosourea derivative with antitumor activity. Similar to carmustine, chlorozotocin, nimustine, ranimustine. Antineoplastic.
Uses
CCNU is an oral anticancer drug that was approved by the U.S. Food and Drug Administration in 1976 for marketing, as lomustine (FDA 2009a). CCNU is used alone or in combination with other antineoplastic agents, including procarbazine and vincristine, etoposide and prednimustine, and other combinations (IARC 1981, HSDB 2009). It is used primarily in the treatment of Hodgkin’s disease and brain tumors, but it has also been used to treat other cancer, includ-ing lung cancer, non-Hodgkin’s lymphoma, malignant melanoma, breast cancer, kidney cancer, and cancer of the gastrointestinal tract (MedlinePlus 2009). It has also been applied to the skin to treat mycosis fungoides and psoriasis.
Uses
Lomustine USP is used to treat Malignant brain tumors; Hodgkin’s disease.
General Description
Lomustine is available in 10-, 40-, and 100-mg capsules fororal administration in the treatment of primary and metastaticbrain cancers and Hodgkin’s lymphoma. This lipophilicagent is well absorbed, widely distributed, and crosses theblood-brain barrier. Lomustine undergoes extensive hepaticmetabolism, which is mediated by CYP3A4 to give severalhydroxylated metabolites, which arise as a result of oxidationof the cyclohexyl ring. Several of these are more activethan the parent compound. Denitrosation and dechlorinationhave also been demonstrated to occur for lomustine as well.The intact drug was not found in plasma when the agent wasadministered orally. Elimination occurs primarily in theurine with an elimination half-life of 16 to 72 hours.Myelosuppression is dose limiting and presents in a mannersimilar to that seen with carmustine. Other toxicities includenausea, vomiting, anorexia, impotence, sterility, amenorrhea,and infertility. Pulmonary and renal toxicity are rarelyseen during standard-dose therapy but increase during highdosetherapy.