Mitomycin C CAS 50-07-7
Introduction：Basic information about Mitomycin C CAS 50-07-7, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Mitomycin C Basic informationdescription Chemical properties Side effects Uses Background
| 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;API;MUTAMYCIN;antibiotic;Amines;Chiral Reagents;Heterocycles;Antibiotic Explorer;Antibiotics;Intermediates & Fine Chemicals;Pharmaceuticals;Antibiotics G-MAntibiotics;AntibioticsStem Cell Expansion;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 |
| 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 |
| Water Solubility | soluble |
| Merck | 14,6215 |
| BRN | 7231816 |
| Stability: | Stable. Incompatible with strong acids, strong bases, strong oxidizing agents. |
| InChI | 1S/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-/m1/s1 |
| InChIKey | NWIBSHFKIJFRCO-WUDYKRTCSA-N |
| 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) |
Safety Information
| Hazard Codes | T,Xn,T+ |
| Risk Statements | 25-40-22-45-26/27/28 |
| Safety Statements | 36/37-45-28A-28-53-22 |
| RIDADR | UN 3462 6.1/PG 2 |
| WGK Germany | 3 |
| RTECS | CN0700000 |
| F | 8-10 |
| TSCA | TSCA listed |
| HazardClass | 6.1(a) |
| PackingGroup | II |
| HS Code | 29419090 |
| Storage Class | 6.1A - Combustible acute toxic Cat. 1 and 2 very toxic hazardous materials |
| Hazard Classifications | Acute Tox. 2 Oral Carc. 2 |
| 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) |
| 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 antibioticand antitumor activities and has been studied extensively sincethe 1950s. A unique feature of this drug is strong bioreductivealkylation under hypoxic conditions. Oxygen-poor cellsinternal to solid tumors provide an environment in which thisdrug is highly activated. As an antitumor agent, it has shownefficacy 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 sideeffectprofile 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 crystallinesolid. |
| 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 anantibiotic that is derived from a species of Streptomyces.It is sometimes classified as an alkylating agent becauseit can covalently bind to and cross-link DNA.Mitomycin is thought to inhibit DNA synthesis throughits ability to alkylate double-strand DNA and bringabout interstrand cross-linking. There is evidence thatenzymatic reduction by a reduced nicotinamide–adenine dinucleotide phosphate (NADPH) dependentreductase is necessary to activate the drug. The drug is rapidly cleared from serum after intravenousinjection 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 ofmitomycin-containing broths by culturing a mitomycin-producing organism,e.g. Streptomyces caespitosus, in suitable media as described at length in theliterature. At the end of the fermentation cycle the whole broth is usuallycentrifuged, filtered or otherwise treated to separate the solids (mycelia) fromthe supernatant which contains substantially all of the antibiotic activity. In commercial processes there is usually a period of time intervening betweenthe end of the fermentation cycle and the time at which the mycelia isactually removed from the broth; such a period may range from severalminutes 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 oflarge quantities of broth, or the time involved in waiting for equipment tobecome available for use. In the commercial preparation of mitomycin, themitomycin-containing whole broths decrease rapidly in potency during thetime following the completion of the fermentation cycle and prior to theremoval of the mycelia. It has been observed that a whole broth will losesubstantially all of its mitomycin activity within about 6 hours at roomtemperature and within about 24 hours at 10°C. It has, however, beendiscovered, as described in US Patent 3,042,582, that in the process for therecovery of mitomycin C from mitomycin C-containing whole broth, the step ofadding about 0.1 wt % with whole broth of sodium lauryl sulfate to the wholebroth at the completion of the fermentation cycle substantially eliminates suchdestruction 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 carcinomasof the stomach, pancreas, colon, breast, and cervix. |
| Side effects | The major toxicity associated with mitomycin therapyis unpredictably long and cumulative myelosuppressionthat affects both white blood cells andplatelets. A syndrome of microangiopathic hemolyticanemia, thrombocytopenia, and renal failure also hasbeen described. Renal, hepatic, and pulmonary toxicitymay occur. The drug is teratogenic and carcinogenic,and it can cause local blistering. |
| Potential Exposure | This compound is an antitumor antibioticcomplex. 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. |
| First aid | If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith soap and water. Seek medical attention immediately. Ifthis chemical has been inhaled, remove from exposure,begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR ifheart action has stopped. Transfer promptly to a medicalfacility. When this chemical has been swallowed, get medical attention. Give large quantities of water and inducevomiting. Do not make an unconscious person vomit. Keepvictim quiet and maintain normal body temperature. |
| Environmental Fate | Mitomycin C is naturally produced by S. caespitosus, a microorganismfound in soil and decaying vegetation. Asa compound potentially released in commercial solid waste orin spill or container residue, mitomycin C is not thought topersist in soil and water. Calculations based on its hydrolysisrate in water at 25 ℃ show a half-life of 12.9 days. It is readilysoluble in water, so mobility in groundwater is high. Mitomycinpersistence 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., HazardClass: 6.1; Labels: 6.1-Poisonous materials, TechnicalName 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 atthe N6 position of adenine and at the O6 and N2 positions ofguanine. In addition, single-strand breakage of DNA is causedby reduced mitomycin C (this can be prevented by free radicalscavengers). Its action is most prominent during the late G1and early S phases of the cell cycle. Mitomycin C can inhibitRNA and protein synthesis at high concentrations. MytomycinC is an aneuploidy-inducing agent. Oxygen and radiationtherapy have been shown to enhance the development oftoxicity. |
| 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, calciumsalts. |
| Waste Disposal | Consult with environmentalregulatory agencies for guidance on acceptable disposalpractices. Generators of waste containing this contaminant(≥100 kg/mo) must conform to EPA regulations governingstorage, transportation, treatment, and waste disposal.It is inappropriate and possibly dangerous to the environmentto dispose of expired or waste drugs and pharmaceuticalsby flushing them down the toilet or discarding themto the trash. Household quantities of expired or wastepharmaceuticals may be mixed with wet cat litter or coffeegrounds, double-bagged in plastic, discard in trash.Larger quantities shall carefully take into considerationapplicable DEA, EPA, and FDA regulations. If possiblereturn the pharmaceutical to the manufacturer for properdisposal being careful to properly label and securely packagethe material. Alternatively, the waste pharmaceuticalshall be labeled, securely packaged, and transported by astate licensed medical waste contractor to dispose byburial in a licensed hazardous or toxic waste landfill orincinerator. |
| Background | Mitomycin C, also known as MMC, is an antitumor antibiotic isolated from Streptomyces caespitosus. When activated, this alkylating agent crosslinks double stranded DNA resulting in DNA damage. Mitomycin C has been found to have lethal effects on HeLa cells during the G1 phase of the cell cycle. DNA damage caused by Mitomycin C can lead to increased levels of p53 that can result in cell cycle arrest or apoptosis. |
| References | [1] ANDREW R TEE Christopher G P. DNA-damaging agents cause inactivation of translational regulators linked to mTOR signalling[J]. Oncogene, 2000, 19 26: 3021-3031. DOI:10.1038/sj.onc.1203622 [2] IN-CHUL PARK . Mitomycin C induces apoptosis in a caspases-dependent and Fas/CD95-independent manner in human gastric adenocarcinoma cells[J]. Cancer letters, 2000, 158 2: Pages 125-132. DOI:10.1016/s0304-3835(00)00489-4 [3] Merck’s Index, Nachtrag 1930. Verlag von E. Merck, Darmstadt. 14 Seiten[J]. Archiv der Pharmazie, 1930, 268 6: 444-445. DOI:10.1002/ardp.19302680608 |
Mitomycin C Preparation Products And Raw materials
| Raw materials | Dichloromethane-->streptomyces avermifilis-->HAM'S F10-MEDIUM |
| Preparation Products | Mitomycin A-->7-Hydroxymitosene |
