| Product Name: | Mitomycin C | | Synonyms: | Mitomycin C(Ametycine);Azirino[2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione, 6-amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-5-methyl-;Mytomycin C;[1aR-(1aα,8β,8aα,8bα)]-6-Amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-5-methylazirino[2',3':3,4]pyrrolo[1,2-α]indole-4,7-dione;6-Amino-1,1a,2,8,8a,8b-hexahydro-8-(hydroxymethyl)-8a-methox-5-methylazirino[2',3':3,4]pyrrolo[1,2-;MitonyycinC;[1aS-(1aα,8β,8aα,8bα)]-6-Amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-5-methylazirino[2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione;8balpha)]-8aalph | | CAS: | 50-07-7 | | MF: | C15H18N4O5 | | MW: | 334.33 | | EINECS: | 200-008-6 | | Product Categories: | Apoptosis Inducers;Anti-cancer&immunity;Amines;API;MUTAMYCIN;antibiotic;Antibiotics;Antibiotic Explorer;Intermediates & Fine Chemicals;Pharmaceuticals;Antibiotics G-MAntibiotics;AntibioticsStem Cell Expansion;Chiral Reagents;Heterocycles;AziridinesStem Cell Biology;DissociationAntibiotics;Interferes with DNA SynthesisMore...Close...;Antibiotics A to;Antibiotics by Application;AntibioticsAntibiotics;Antineoplastic and Immunosuppressive AntibioticsAntibiotics;Cell Culture;Chemical Structure Class;Culture;Mechanism of Action;Reagents and Supplements;Stem Cell Isolation;AziridinesAntibiotics;Core Bioreagents;Interferes with DNA Synthesis;Research Essentials | | Mol File: | 50-07-7.mol |  |
| | Mitomycin C Chemical Properties |
| 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 | | pka | pKa 2.8(H2O,t =25,I=0.1) (Uncertain) | | form | powder | | color | blue-gray | | PH | pH (0.5 g/l, 25℃ : )5.0～7.0 | | Water Solubility | soluble | | Merck | 14,6215 | | BRN | 7231816 | | Stability: | Stable. Incompatible with strong acids, strong bases, strong oxidizing agents. | | CAS DataBase Reference | 50-07-7(CAS DataBase Reference) | | IARC | 2B (Vol. 10, Sup 7) 1987 | | EPA Substance Registry System | Mitomycin C (50-07-7) |
| Provider | Language |
|
[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
| English |
|
SigmaAldrich
| English |
| | Mitomycin C Usage And Synthesis |
| 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. | | Description | Mitomycin C is naturally produced by Streptomyces caespitosus,
an Actinobacteria found in soil. Mitomycin C has antibiotic
and antitumor activities and has been studied extensively since
the 1950s. A unique feature of this drug is strong bioreductive
alkylation under hypoxic conditions. Oxygen-poor cells
internal to solid tumors provide an environment in which this
drug is highly activated. As an antitumor agent, it has shown
efficacy in a wide variety of cancers, including gastric cancer,
pancreatic cancer, breast cancer, non-small-cell lung cancer,
cervical cancer, prostate cancer, and bladder cancer. The sideeffect
profile is large, which prohibits its widespread use.
Mitomycin C is antibacterial to gram-positive, gram-negative,
and acid-fast bacilli. | | Chemical Properties | Blue-violet crystals or crystalline powder. | | Chemical Properties | Mitomycin is a blue-violet crystalline
solid. | | Originator | Mitomycin,Medac,W. Germany,1960 | | Uses | Mitomycin C USP (Mutamycin) is used to treat chronic myelogenous leukemia; reticulum cell sarcoma; Hodgkin.s disease; non-Hodgkin.s lymphomas; cancer of stomach, pancreas, lung; epithelial tumors. | | Uses | An antitumor antibiotic. It is used as antineoplastic. | | Uses | Mitomycin C is the most studied of a family of highly distinctive blue/purple metabolites produced by several Streptomyces species. Mitomyin C exhibits potent antibacterial and antitumour activity and inhibits DNA synthesis by intercalation, blocking nuclear division with the induction of apoptosis in cancer cells. | | 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. | | Definition | Antibiotic derivedfrom Streptomyces, stated to be effective againsttumors. | | 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 | | General Description | Blue-violet crystals. Used as an anti-tumor antibiotic complex. | | General Description | administration in the treatment of cancers of the stomachand pancreas when other treatments have failed. Other useshave included breast, NSCLC, cervical, bladder, and headand neck cancers. Mechanisms of resistance include increasedsynthesis of nucleophilic detoxifying compoundssuch as glutathione, decreased expression of activating enzymessuch as DT-diaphorase, and increased efflux by Pgp.The drug is rapidly cleared from the plasma after administrationand widely distributed but does not cross the bloodbrainbarrier. The parent and metabolites are excretedmainly in the feces with an elimination half-life of 50 minutes.Adverse effects include dose-limiting myelosuppression,mild nausea and vomiting,. | | General Description | Mitomycin C was isolated from Streptomyces caespitosus in 1958 by Japanese workers and is considered the prototype of the bioreductive alkylating agents. Mitomycin is sometimes included as an alkylating agent but is included here because. It was reasoned that selective activation could be achieved in a reductive environment such as that found in an area of low oxygen content. This is known to occur in tumors where the fast-growing cells often grow beyond the blood supply that would normally provide oxygen. Mitomycin C is capable of being activated and alkylating DNA in an anaerobic environment. The drug contains what would appear to be reactive functionalities, including the quinone and aziridine functionalities, both or which would be thought to be susceptible to nucleophilic attack; however, the reactivity of these functionalities is reduced because of steric and electronic effects in the parent molecule. It was reasoned that selective activation could be achieved in a reductive environment such as that found in an area of low oxygen content. This is known to occur in tumors where the fast-growing cells often grow beyond the blood supply that would normally provide oxygen.A normal cell would undergo apoptosis under these conditions, but because cancer cells often have their apoptotic mechanisms inhibited they continue to survive with little or no oxygen available. Mitomycin C is capable of being activated and alkylating DNA in an anaerobic environment, but there is actually little selectivity for hypoxic cells. Activation can occur enzymatically by both one- and twoelectron processes. Reductive enzymes such as NADPHCYP reductase and DT-diaphorase have been implicated in these processes.Involvement of one-electron processes such as those seen for the anthracylines result in redox cycling and the production of ROS that may result in DNA damage, but the cytotoxicity of mitomycin C is primarily associated with its ability to alkylate DNA. | | Air & Water Reactions | Water soluble. | | Reactivity Profile | Mitomycin C is sensitive to prolonged exposure to light. Mitomycin C may be sensitive to prolonged exposure to air. Mitomycin C is incompatible with strong oxidizing agents, strong acids and strong bases. Calcium salts may cause decomposition. | | 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. | | Fire Hazard | Flash point data for Mitomycin C are not available; however, Mitomycin C is probably combustible. | | 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. | | Side effects | The major toxicity associated with mitomycin therapy
is unpredictably long and cumulative myelosuppression
that affects both white blood cells and
platelets. A syndrome of microangiopathic hemolytic
anemia, thrombocytopenia, and renal failure also has
been described. Renal, hepatic, and pulmonary toxicity
may occur. The drug is teratogenic and carcinogenic,
and it can cause local blistering. | | Potential Exposure | This compound is an antitumor antibiotic
complex. This drug is usually injected intravenously. | | 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 | | 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. | | 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. | | 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. | | 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 |
| | Mitomycin C Preparation Products And Raw materials |
|
