| Identification | More | [Name]
Mitomycin C | [CAS]
50-07-7 | [Synonyms]
[1ar-(1aalpha,8beta,8aalpha,8balpha)]-6-amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-5-methylazirino[2',3':3,4]pyrrolo[1,2-alpha]indole-4,7-dione
6-amino-1,1a,2,8,8a,8b-hexahydro-8-(hydroxymethyl)-8a-methoxy-5-methylazirino[2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione carbamate (ester)
AMETYCIN
MITOCIN C
MITOMYCIN
MITOMYCIN C
MITOMYCIN C, STREPTOMYCES CAESPITOSUS
MMC
MUTAMYCIN
)methyl)-1,1a,2,8,8a,8b-hexahydro-8-a-methoxy-5-methyl-,(1as-(1aalpha,8beta,
7-amino-9-alpha-methoxymitosane
8aalpha,8balpha))-(9ci)
8balpha)]-8aalph
ametycine
azirino(2’,3’:3,4)pyrrolo(1,2-a)indole-4,7-dione,6-amino-1,1a,2,8,8a,8b-hexahy
azirino(2’,3’:3,4)pyrrolo(1,2-a)indole-4,7-dione,6-amino-8-(((aminocarbonyl)oxy
azirino[2’,3’:3,4]pyrrolo[1,2-a]indole-4,7-dione,6-amino-8-[[(aminocarbonyl)ox
mitomycinum
mitomycynac
mitomycynac(polish) | [EINECS(EC#)]
200-008-6 | [Molecular Formula]
C15H18N4O5 | [MDL Number]
MFCD00078109 | [Molecular Weight]
334.33 | [MOL File]
50-07-7.mol |
| Chemical Properties | Back Directory | [Definition]
Antibiotic derivedfrom Streptomyces, stated to be effective againsttumors. | [Appearance]
Mitomycin is a blue-violet crystalline
solid. | [Melting point ]
360 °C | [Boiling point ]
471.14°C (rough estimate) | [density ]
1.2238 (rough estimate) | [refractive index ]
1.6800 (estimate) | [storage temp. ]
2-8°C
| [solubility ]
H2O: 4 mL/vial Stock solutions should be filter sterilized and stored at 2-8 °C in the dark., clear to slightly hazy, blue to purple
| [form ]
powder
| [pka]
pKa 2.8(H2O,t =25,I=0.1) (Uncertain) | [color ]
blue-gray
| [PH]
pH (0.5 g/l, 25℃ : )5.0～7.0 | [Stability:]
Stable. Incompatible with strong acids, strong bases, strong oxidizing agents. | [Water Solubility ]
soluble | [Usage]
An antitumor antibiotic | [Merck ]
13,6236 | [BRN ]
7231816 | [CAS DataBase Reference]
50-07-7(CAS DataBase Reference) | [IARC]
2B (Vol. 10, Sup 7) 1987 | [EPA Substance Registry System]
50-07-7(EPA Substance) |
| Safety Data | Back Directory | [Hazard Codes ]
T,Xn,T+ | [Risk Statements ]
R25:Toxic if swallowed.
R40:Limited evidence of a carcinogenic effect.
R22:Harmful if swallowed.
R45:May cause cancer.
R26/27/28:Very Toxic by inhalation, in contact with skin and if swallowed . | [Safety Statements ]
S36/37:Wear suitable protective clothing and gloves .
S45:In case of accident or if you feel unwell, seek medical advice immediately (show label where possible) .
S28:After contact with skin, wash immediately with plenty of ... (to be specified by the manufacturer) .
S53:Avoid exposure-obtain special instruction before use .
S22:Do not breathe dust . | [RIDADR ]
UN 3462 6.1/PG 2
| [WGK Germany ]
3
| [RTECS ]
CN0700000
| [F ]
8-10 | [TSCA ]
Yes | [HazardClass ]
6.1(a) | [PackingGroup ]
II | [HS Code ]
29419090 | [Hazardous Substances Data]
50-07-7(Hazardous Substances Data) | [Toxicity]
LD50 i.v. in mice: 5 mg/kg (Wakaki); also reported as 9 mg/kg (Kinoshita) |
| Hazard Information | Back Directory | [General Description]
Blue-violet crystals. Used as an anti-tumor antibiotic complex. | [Reactivity Profile]
MITOMYCIN C(50-07-7) is sensitive to prolonged exposure to light. MITOMYCIN C(50-07-7) may be sensitive to prolonged exposure to air. This chemical is incompatible with strong oxidizing agents, strong acids and strong bases. Calcium salts may cause decomposition. | [Air & Water Reactions]
Water soluble. | [Hazard]
Possible carcinogen. | [Health Hazard]
Toxic doses as low as 750 mg/kg have been reported in humans. The major toxic effect is myelosuppression, characterized by marked leukopenia and thrombocytopenia; this may be delayed and cumulative. Interstitial pneumonia and glomerular damage resulting in kidney failure are unusual but well documented complications. Lung conditions--administration of mitomycin has been recognized as causing pneumonitis, alveolitis and pulmonary fibrosis. Kidney conditions--administration of mitomycin can cause kidney damage. Kidney toxicity was observed in 1-5 percent of patients. Depressed immune conditions. | [Potential Exposure]
This compound is an antitumor antibiotic
complex. This drug is usually injected intravenously. | [Fire Hazard]
Flash point data for this chemical are not available; however, MITOMYCIN C is probably combustible. | [First aid]
Move victim to fresh air. Call 911 or emergency
medical service. Give artificial respiration if victim is not
breathing. Do not use mouth-to-mouth method if victim
ingested or inhaled the substance; give artificial respiration
with the aid of a pocket mask equipped with a one-way
valve or other proper respiratory medical device.
Administer oxygen if breathing is difficult. Remove and isolate
contaminated clothing and shoes. In case of contact
with substance, immediately flush skin or eyes with running
water for at least 20 minutes. For minor skin contact, avoid
spreading material on unaffected skin. Keep victim warm
and quiet. Effects of exposure (inhalation, ingestion, or skin
contact) to substance may be delayed. Ensure that medical
personnel are aware of the material(s) involved and take
precautions to protect themselves. Medical observation is
recommended for 24 to 48 hours after breathing overexposure,
as pulmonary edema may be delayed. As first aid for
pulmonary edema, a doctor or authorized paramedic may
consider administering a drug or other inhalation therapy. | [Shipping]
UN2811 Toxic solids, organic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials, Technical
Name Required. UN3249 Medicine, solid, toxic, n.o.s.,
Hazard Class: 6.1; Labels: 6.1-Poisonous materials. | [Incompatibilities]
Incompatible with oxidizers (chlorates,
nitrates, peroxides, permanganates, perchlorates, chlorine,
bromine, fluorine, etc.); contact may cause fires or explosions.
Keep away from alkaline materials, strong bases,
strong acids, oxoacids, epoxides, heat, strong light, calcium
salts. | [Waste Disposal]
Consult with environmental
regulatory agencies for guidance on acceptable disposal
practices. Generators of waste containing this contaminant
(≥100 kg/mo) must conform to EPA regulations governing
storage, transportation, treatment, and waste disposal.
It is inappropriate and possibly dangerous to the environment
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, double-bagged 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. | [Originator]
Mitomycin,Medac,W. Germany,1960 | [Indications]
Mitomycin (mitomycin C, Mitocin-C, Mutamycin) is an
antibiotic that is derived from a species of Streptomyces.
It is sometimes classified as an alkylating agent because
it can covalently bind to and cross-link DNA.
Mitomycin is thought to inhibit DNA synthesis through
its ability to alkylate double-strand DNA and bring
about interstrand cross-linking. There is evidence that
enzymatic reduction by a reduced nicotinamide–
adenine dinucleotide phosphate (NADPH) dependent
reductase is necessary to activate the drug.
The drug is rapidly cleared from serum after intravenous
injection but is not distributed to the brain. | [Manufacturing Process]
The commercial production of mitomycin involves the preparation of
mitomycin-containing broths by culturing a mitomycin-producing organism,
e.g. Streptomyces caespitosus, in suitable media as described at length in the
literature. At the end of the fermentation cycle the whole broth is usually
centrifuged, filtered or otherwise treated to separate the solids (mycelia) from
the supernatant which contains substantially all of the antibiotic activity.
In commercial processes there is usually a period of time intervening between
the end of the fermentation cycle and the time at which the mycelia is
actually removed from the broth; such a period may range from several
minutes to several hours in length and may be due to a number of factors,
e.g., the time necessary to conduct the actual centrifugation or filtration of
large quantities of broth, or the time involved in waiting for equipment to
become available for use. In the commercial preparation of mitomycin, the
mitomycin-containing whole broths decrease rapidly in potency during the
time following the completion of the fermentation cycle and prior to the
removal of the mycelia. It has been observed that a whole broth will lose
substantially all of its mitomycin activity within about 6 hours at room
temperature and within about 24 hours at 10°C. It has, however, been
discovered, as described in US Patent 3,042,582, that in the process for the
recovery of mitomycin C from mitomycin C-containing whole broth, the step of
adding about 0.1 wt % with whole broth of sodium lauryl sulfate to the whole
broth at the completion of the fermentation cycle substantially eliminates such
destruction of mitomycin C by mitase. | [Brand name]
Mutamycin (Bristol-Myers Squibb);Mytozytrex (SuperGen). | [Therapeutic Function]
Cancer chemotherapy | [Biological Activity]
Antibiotic and antitumor agent. Covalently binds DNA forming intra- and interstrand crosslinks. Inhibits DNA synthesis. | [Clinical Use]
Mitomycin has limited palliative effects in carcinomas
of the stomach, pancreas, colon, breast, and cervix. | [Drug interactions]
Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine (increased risk
of agranulocytosis).
Live vaccines: risk of generalised infections - avoid. | [Environmental Fate]
Mitomycin C is naturally produced by S. caespitosus, a microorganism
found in soil and decaying vegetation. As
a compound potentially released in commercial solid waste or
in spill or container residue, mitomycin C is not thought to
persist in soil and water. Calculations based on its hydrolysis
rate in water at 25 ℃ show a half-life of 12.9 days. It is readily
soluble in water, so mobility in groundwater is high. Mitomycin
persistence in air is low and bioaccumulation is low. | [Metabolism]
Mitomycin is administered IV in the treatment of disseminated adenocarcinoma of the stomach or pancreas, and it has been used intravesically in superficial bladder cancer. Biotransformation pathways are saturable, and approximately 10% of an administered dose is eliminated unchanged via the kidneys. | [storage]
+4°C | [Purification Methods]
Mitomycin C forms blue-violet crystals from *C6H6/pet ether. It is soluble in Me2CO, MeOH and H2O, moderately soluble in *C6H6, CCl4 and Et2O but insoluble in pet ether. It has UV max at 216, 360 and a weak peak at 560nm in MeOH. [Stevens et al. J Med Chem 8 1 1965, Shirahata & Hirayama J Am Chem Soc 105 7199 1983, Beilstein 25 III/IV 516.] | [Toxicity evaluation]
Mitomycin C inhibits DNA synthesis and cross-links DNA at
the N6 position of adenine and at the O6 and N2 positions of
guanine. In addition, single-strand breakage of DNA is caused
by reduced mitomycin C (this can be prevented by free radical
scavengers). Its action is most prominent during the late G1
and early S phases of the cell cycle. Mitomycin C can inhibit
RNA and protein synthesis at high concentrations. Mytomycin
C is an aneuploidy-inducing agent. Oxygen and radiation
therapy have been shown to enhance the development of
toxicity. | [References]
1) Tee and Proud (2000), DNA-damaging agents cause inactivation of translational regulators linked to mTOR signaling; Oncogene, 30 21
2) Park et al. (2000), Mitomycin C induces apoptosis in a caspases-dependent and Fas/CD95- independent manner in human gastric adenocarcinoma cells; Cancer Lett., 158 125
3) Merck Index 14:6215 |
| Material Safety Data Sheet(MSDS) | Back Directory | [msds information]
[1aR-(1aalpha,8beta,8aalpha,8balpha)]-6-Amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-5-methylazirino[2',3':3,4]pyrrolo[1,2-alpha]indole-4,7-dione(50-07-7).msds |
| Questions And Answer | Back Directory | [description]
Mitomycin C (MMC), an antineoplastic antibiotic derived from Streptomyces caespitosus or Streptomyces lavendulae, is a cell cycle-specific alkylating agent, inhibits DNA synthesis through covalent mitomycin C-DNA adduct with EC50 values of 0.14μM in PC3 cells. Therefore, it was served as a chemotherapeutic agent that has demonstrated its antitumor activity and has been used widely in treatment of various cancers.
Although it is active against a wide variety of tumors, newer agents have largely replaced MMC except in anal cancer; outside of the United States, MMC is infrequently used for treatment of advanced non-small cell lung cancer (NSCLC), and breast cancer. | [Chemical properties]
It is a crystalline powder or a powder with blue-purple shiny crystal. Its solid state is stable, while easily deactivated in acidic and alkaline solution. Mp> 360 ℃; the maximum absorption wavelength in methanol is 216nm, 360nm and 560nm.The maximum absorption wavelength in aqueous solution is 365nm ± 2nm. This product is soluble in water, methanol, acetone and ethyl acetate and other organic solvents, slightly soluble in benzene, ether and carbon tetrachloride, insoluble in petroleum ether. Highly toxic chemical, LD50 (rat, oral) 14mg/kg. Tests show that this product has potential carcinogenic effects on experimental animals. | [Side effects]
As with many other chemotherapeutic agents, most of the side effects of Mitomycin C (MMC) are dose-related, including myelosuppression (which is typically delayed in onset), nausea, vomiting, diarrhea, stomatitis, dementia, and alopecia. Pulmonary toxicity associated with MMC is unpredictable, but more likely to occur at higher doses.
The following side effects are common (occurring in greater than 30%) for patients taking Mitomycin C:
Low blood counts. Your white and red blood cells and platelets may temporarily decrease. This can put you at increased risk for infection, anemia and/or bleeding. The nadir counts are delayed with this drug.
Nadir: Meaning low point, nadir is the point in time between chemotherapy cycles in which you experience low blood counts.
Onset: 3 weeks
Nadir: 4-6 weeks
Recovery: 6-8 weeks
Mouth sores
Poor appetite
Fatigue
These side effects are less common side effects (occurring in about 10-29%) of patients receiving Mitomycin C:
Nausea and vomiting, usually mild
Diarrhea
Hair loss
Bladder inflammation (urinary frequency, burning, cramping, pain)-seen with intravesical (into the bladder) therapy. | [Uses]
(1) It is a cell division inhibitors, nucleic acid inhibitors and phage inducer; an anti-tumor drugs in clinical use.
(2) This drug has a broad anti-tumor spectrum, and effective for gastric cancer, breast cancer. It has a certain effect on lung cancer, liver cancer, malignant lymphoma, Hodgkin's disease, reticular cell sarcoma, uterine cancer, leukemia, intestinal cancer and pancreatic cancer, but with a short remission. Combination with urokinase can improve the efficacy. The goods exert its function quickly, but the number of operators is not high, and it has a high toxicity. The goods and bleomycin as well as its derivatives ——doxorubicin are anti-cancer drugs of antibiotic which can disrupt DNA. It can depolymerize DNA in the cell, inhibit DNA replication in proliferating cell. The LD50 of intravenous injection of mice is 5ml/kg. It acts as an anticancer drugs, commonly used in the treatment of digestive system cancers. |
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