13909-09-6 Usage
Description
SEMUSTINE, also known as Me-CCNU [1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea], is an alkylating agent of the nitrosourea group. It is a crystalline solid or light yellow powder and has been classified as 'carcinogenic to humans' by the International Agency for Research on Cancer. SEMUSTINE functions as an antineoplastic agent, undergoing spontaneous chemical decomposition to yield electrophilic compounds, which induce alkylation and carbamoylation of cellular macromolecules, including DNA and protein.
Uses
Used in Anticancer Applications:
SEMUSTINE is used as an antineoplastic agent for the treatment of various types of cancers, including primary and metastatic brain tumors, Lewis lung tumor, L1210 leukemia, Hodgkin's disease, malignant gliomas, gastrointestinal tract adenocarcinomas, breast carcinomas, squamous-cell carcinomas, malignant melanoma, and epidermoid carcinoma of the lung. It is also used in combination with other chemotherapeutic agents to enhance the treatment efficacy.
Used in Pharmacological Studies:
SEMUSTINE is used in pharmacological studies for nutrient-sensitized screening for drugs that shift the energy metabolism from mitochondrial respiration to glycolysis, in the CEOP regimen as induction chemotherapy in patients with lymphoma, and in investigations for its use in chemotherapy.
Used in Drug Design:
An emerging trend in the field of cancer treatment is the design of hybrid steroid compounds of anticancer agents, such as SEMUSTINE. These compounds are believed to produce less toxicity and significantly lower cytotoxic components alone, while increasing the anticancer activity of alkylating esters.
Used in Antihyperlipidemic Applications:
SEMUSTINE is also used as an antihyperlipidemic agent, contributing to the management of lipid levels in the body.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
A halogenated and nitrated amide. Organic amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).
Fire Hazard
Flash point data for SEMUSTINE are not available. SEMUSTINE is probably combustible.
Safety Profile
Confirmed human
carcinogen producing leukemia.
Experimental carcinogenic and tumorigenic
data. Poison by ingestion, intraperitoneal,
intravenous, and possibly other routes.
Mutation data reported. Human systemic
effects by ingestion: nausea or vomiting,
damage to kidney tubules and glomeruli, and
hematuria (blood in the urine). When heated
to decomposition it emits very toxic fumes
of Cland NOx. See also N-NITROSO
COMPOUNDS.
Potential Exposure
Semustine is chemotherapy agent; an antineoplastic agent which functions as an alkylating agent.
Carcinogenicity
1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.
Environmental Fate
Semustine is released to the environment through a number of
routes because of its production and use as an antineoplastic
agent. Semustine is an alkylating agent that may hydrolyze
under environmental conditions. Upon its released into air,
semustine will exist in both the vapor and particulate phases in
the atmosphere because of its estimated vapor pressure of
5.6 × 10-6 mm Hg at 25 ℃. Semustine when in vapor phase
will be degraded by reaction with photochemically produced
hydroxyl radicals in the atmosphere (estimated half-life for this
reaction in air is approximately 16 h). Particulate-phase
semustine is removed via wet or dry deposition. Semustine
chromophores (absorbs at 290 nm) are susceptible to direct
photolysis by sunlight. If released to soil, semustine is expected
to have moderate mobility based on an estimated Koc of 330.
Volatilization from moist soil surfaces is not expected to be an
important fate process based on an estimated Henry’s Law
constant of 2.5 ×10-10 atm-cu m mol-1. Biodegradation data
for this compound are not available. Semustine is expected to
adsorb to suspended solids and sediment based on release into
water (based on estimated Koc). Based on this compound’s
estimated Henry’s Law constant, volatilization from water
surfaces is not expected to be an important fate process. An
estimated bioconcentration factor of 70 suggests moderate
bioconcentration in aquatic organisms. Occupational exposure
to semustine is very likely via skin contact at workplaces where
semustine is produced or used. The general population is highly
unlikely to be exposed to this compound unless receiving
specific treatment with semustine as an antineoplastic agent.
Based on the overall literature, it appears that some pharmaceutically
active compounds originating from human or
veterinary therapy are not completely eliminated in municipal
sewage treatment plants and are therefore discharged into
receiving waters. Wastewater treatment processes often were
not designed to remove them from the effluent. Selected
organic waste compounds may be degrading to new and more
persistent compounds that may be released instead of or in
addition to the parent compound.
Shipping
UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials. PG II.
Toxicity evaluation
Me-CCNU exerts its toxicity by cross-linking with DNA or
DNA-alkylation, carbamoylation of proteins besides DNA
strand breakage. It is cytotoxic in all stages of the cell cycle.
Phenobarbital (PB) pretreatment increases nephrotoxicity of
this compound, suggesting enhanced metabolism of this
compound coupled with generation of reactive intermediates.
PB pretreatment is also known to cause increased alkylation
of both liver and kidney macromolecules and an increase in
the urinary clearance of ethylene-labeled Me-CCNU. Modulation
of liver biotransformation influenced the level of
covalent binding and alkylation, which correlated with the
degree of Me-CCNU-induced nephrotoxicity. Evidence in
favor of Me-CCNU liver biotransformation came from an in
vivo/in vitro colony-forming assay that demonstrated the
presence of a cytotoxic metabolite in the bile of a Me-
CCNU-administered rat. These studies suggest that hepatic
metabolism contributes significantly to the alkylating activity
of Me-CCNU in the liver and the kidney, and indicate that
a liver-derived metabolite may be responsible for the renal
toxicity of Me-CCNU.
Incompatibilities
Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from strong acids, alkaline materials, strong bases. Semustine, an organic amide, reacts with azo and diazo compounds, releasing toxic gases. Amides are very weak bases but they can react as acids, forming salts. Contact with reducing agents can release flammable gases. Mixing amides with dehydrating agents such as such as phosphorus pentoxide or thionyl chloride generates the corresponding nitrile.
Waste Disposal
It is inappropriate to dispose of expired or waste drugs and pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, doublebagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
Check Digit Verification of cas no
The CAS Registry Mumber 13909-09-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,3,9,0 and 9 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 13909-09:
(7*1)+(6*3)+(5*9)+(4*0)+(3*9)+(2*0)+(1*9)=106
106 % 10 = 6
So 13909-09-6 is a valid CAS Registry Number.
InChI:InChI=1/C11H19ClN2O2/c1-9-2-4-10(5-3-9)13-11(16)14(8-15)7-6-12/h8-10H,2-7H2,1H3,(H,13,16)
13909-09-6Relevant articles and documents
Tin(IV) chloride-sodium nitrite as a new nitrosating agent for N-nitrosation of amines, amides and ureas under mild and heterogeneous conditions
Celaries, Benoit,Parkanyi, Cyril
, p. 2371 - 2375 (2008/02/03)
We have developed a new method of N-nitrosation of various secondary and tertiary amines, amides and ureas using a mixture of tin(IV) chloride and sodium nitrate. This method leads to a selective, high-yielding and mild heterogeneous N-nitrosation by in situ generation of nitrosyl chloride (NOCl). The reaction can be carried out in several different solvents such as chloroform, dichloromethane, ethers, ethyl acetate and alcohols, at room temperature. Georg Thieme Verlag Stuttgart.