50-07-7 Usage
Description
Mitomycin C, also known as Mutamycin, is a naturally produced antibiotic and antitumor agent derived from Streptomyces caespitosus, an Actinobacteria found in soil. It has been studied extensively since the 1950s and is known for its strong bioreductive alkylation under hypoxic conditions, making it highly activated in oxygen-poor cells within solid tumors. Mitomycin C exhibits potent antibacterial and antitumor activity, inhibiting DNA synthesis by intercalation and blocking nuclear division with the induction of apoptosis in cancer cells.
Uses
Used in Oncology:
Mitomycin C is used as an anti-tumor drug for a wide variety of cancers, including gastric cancer, pancreatic cancer, breast cancer, non-small-cell lung cancer, cervical cancer, prostate cancer, and bladder cancer. It is particularly effective in treating chronic myelogenous leukemia, reticulum cell sarcoma, Hodgkin's disease, and non-Hodgkin's lymphomas.
Used in Antimicrobial Applications:
Mitomycin C exhibits antibacterial properties against gram-positive, gram-negative, and acid-fast bacilli, making it useful in treating various bacterial infections.
Used in Pharmaceutical Industry:
Mitomycin C is used as a cell division inhibitor, nucleic acid inhibitor, and phage inducer in the development of pharmaceutical products. It is also combined with other anti-cancer drugs, such as bleomycin and doxorubicin, to enhance their efficacy and disrupt DNA replication in proliferating cells.
However, the side effect profile of Mitomycin C is large, which limits its widespread use. It has a high toxicity, and the number of operators is not high, requiring careful administration and monitoring during treatment.
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.
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.
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.
Therapeutic Function
Cancer chemotherapy
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.
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.
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
Check Digit Verification of cas no
The CAS Registry Mumber 50-07-7 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 0 respectively; the second part has 2 digits, 0 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 50-07:
(4*5)+(3*0)+(2*0)+(1*7)=27
27 % 10 = 7
So 50-07-7 is a valid CAS Registry Number.
InChI:InChI=1/C15H18N4O5/c1-5-9(16)12(21)8-6(4-24-14(17)22)15(23-2)13-7(18-13)3-19(15)10(8)11(5)20/h6-7,13,18H,3-4,16H2,1-2H3,(H2,17,22)/t6-,7?,13+,15-/m0/s1
50-07-7Relevant articles and documents
λ-Radiolysis of mitomycin C derivatives
Kuroda,Hisamura,Nakamizo,Otsuji
, p. 53 - 56 (1994)
The λ-Radiolysis reactions of mitomycin C (1) and its derivatives were studied in the hope of developing a radiation-induced drug (RID). The λ- radiolysis reactions were carried out in aqueous solutions under the condition where hydrated electron (e-(aq)) was generated as a principal reactive species. The competitive λ-radiolysis studies revealed that the rate constants for the reactions of 1 with e-(aq) at room temperature was 3.6 x 1010 dm3 mol-1s-1. Among mitomycin C derivatives, the 5H-6- alkoxyimino derivatives 11 and 12, and compound 13 in which ring A of 1 has the 4-hydroxy-6-hydroxyimino structure cleaved to give 1. The mechanic aspect of these λ-radiolysis reactions is discussed.
MITOMYCIN C PRODRUG LIPOSOME FORMULATIONS AND USES THEREOF
-
Paragraph 0110, (2018/05/27)
The present invention provides MMC prodrug compounds and liposomal MMC prodrugs and compositions thereof for the treatment of cancer. The compositions include liposomes containing a phosphatidylcholine lipid, a sterol, a PEG-lipid and a MMC prodrug. The present invention also provides liposomal compositions for the treatment of cancer comprising administering to a patient in need thereof a liposome, wherein the liposome comprises: a phosphatidylcholine lipid; a sterol; a PEG-lipid and a MMC prodrug or a pharmaceutically-acceptable salt thereof.
THERAPEUTIC FOR HEPATIC CANCER
-
, (2011/02/18)
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
Pigs and pig cells having an inactivated α 1,3-galactosyl transferase gene
-
, (2008/06/13)
Human pre-formed xenoantibodies play an important role in the hyperacute rejection response in human xenotransplantation. Disclosed are materials and methods for removing or neutralizing such antibodies. Also disclosed are materials and methods for reducing or eliminating the epitopes in the donor organs that are recognized by such antibodies. Such epitopes are formed as the result of activity by the enzyme α-1,3 galactosyltransferase. The porcine gene encoding α-1,3 galactosyltransferase is disclosed, as are materials and methods for inactivating (“knocking out”) the α-1,3 galactosyltransferase gene in mammalian cells and embryos. Included are nucleic acid constructs useful for inactivating the α-1,3 galactosyltransferase gene in a target cell. Also disclosed is a novel leukemia inhibitory factor (T-LIF) that is useful for maintenance of embryonic stem cells and primordial germ cells in culture.
