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Identification
Name Mitomycin
Accession Number DB00305 (APRD00284)
Type small molecule
Groups approved
Description

An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional alkylating agents causing cross-linking of DNA and inhibition of DNA synthesis. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
7-Amino-9α-methoxymitosane
Mitamycin
MMC
Salts Not Available
Brand names
Name Company
Ametycin
Ametycine
Mit-C
Mito-C
Mitocin-C
Mitomycin (TN)
Mitomycin C
Mitomycin-C
Mitomycinum
Mitomycinum C
Mitomycyna C [Polish]
Mitosol Mobius Therapeutics, LLC
Mitozytrex
Muamycin
Mutamycin
Mytomycin
Mytozytrex
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Brand mixtures Not Available
Categories
  • Nucleic Acid Synthesis Inhibitors
  • Antibiotics, Antineoplastic
  • Alkylating Agents
  • Cross-Linking Reagents
CAS number 50-07-7
Weight Average: 334.3272
Monoisotopic: 334.127719706
Chemical Formula C15H18N4O5
InChI Key InChIKey=NWIBSHFKIJFRCO-WUDYKRTCSA-N
InChI
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
Plain Text
IUPAC Name
[(4S,6S,7R,8S)-11-amino-7-methoxy-12-methyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.0^{2,7}.0^{4,6}]trideca-1(9),11-dien-8-yl]methyl carbamate
SMILES
CO[C@]12[C@H]3N[C@H]3CN1C1=C([C@H]2COC(N)=O)C(=O)C(N)=C(C)C1=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Mitomycins
Substructures
  • Indolequinones
  • Carbamates and Derivatives
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Azirines
  • Benzoquinones
  • Piperazines
  • Pyrrolidines
  • Ethers
  • Aminals and Derivatives
  • Enamines
  • Heterocyclic compounds
  • Mitomycins
  • Pyrrolines
  • Ketones
Pharmacology
Indication For treatment of malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, and urinary bladder. Also used as an adjunct to ab externo glaucoma surgery.
Pharmacodynamics Mitomycin is one of the older chemotherapy drugs, which has been around and in use for decades. It is an antibiotic which has been shown to have antitumor activity. Mitomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Mitomycin has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2.
Mechanism of action Mitomycin is activated in vivo to a bifunctional and trifunctional alkylating agent. Binding to DNA leads to cross-linking and inhibition of DNA synthesis and function. Mitomycin is cell cycle phase-nonspecific.
Absorption Erratic.
Volume of distribution Not Available
Protein binding Not Available
Metabolism Primarily hepatic, some in various other tissues.
Route of elimination Approximately 10% of a dose of mitomycin is excreted unchanged in the urine.
Half life 8-48 min
Clearance Not Available
Toxicity Oral, mouse: LD50 = 23 mg/kg; Oral, rat: LD50 = 30 mg/kg. Symptoms of overdose include nausea and vomiting.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Accord healthcare inc
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Supergen inc
  • Bristol laboratories inc div bristol myers co
  • Bristol myers co
Packagers
Dosage forms
Form Route Strength
Injection, powder, lyophilized, for solution Topical 0.2 mg/mL
Powder, for solution Intravesical
Prices
Unit description Cost Unit
Mutamycin 40 mg vial 878.48 USD vial
Mutamycin 20 mg vial 434.8 USD vial
Mitomycin 40 mg vial 300.0 USD vial
Mitomycin 20 mg vial 142.55 USD vial
Mutamycin 5 mg vial 128.75 USD vial
Mitomycin 5 mg vial 52.43 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point >360 °C PhysProp
boiling point 534 °C PhysProp
water solubility Soluble (8430 mg/L) Not Available
logP -0.40 HANSCH,C ET AL. (1995)
pKa 10.9 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 1.01e+01 g/l ALOGPS
logP -0.55 ALOGPS
logP -3 ChemAxon
logS -1.5 ALOGPS
pKa (strongest acidic) -0.3 ChemAxon
pKa (strongest basic) 6.8 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 146.89 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 83.27 ChemAxon
polarizability 32.77 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00208 Link_out
KEGG Compound C06681 Link_out
PubChem Compound 5746 Link_out
PubChem Substance 46508353 Link_out
ChemSpider 5544 Link_out
ChEBI 27504 Link_out
ChEMBL 27504 Link_out
Therapeutic Targets Database DAP001402 Link_out
PharmGKB PA450524 Link_out
Drug Product Database 2230729 Link_out
RxList http://www.rxlist.com/cgi/generic3/mitomycin.htm Link_out
Drugs.com http://www.drugs.com/cdi/mitomycin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Mitomycin Link_out
ATC Codes
  • L01DC03
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label show (82.3 KB)
MSDS show (77.9 KB)
Interactions
Drug Interactions
Drug Interaction
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Vinblastine Potentially severe lung toxicity
Vincristine Potentially severe lung toxicity
Vindesine Potentially severe lung toxicity
Food Interactions Not Available
Targets

1. DNA

Pharmacological action: yes
Actions: antagonist, cross-linking/alkylation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Rodighiero G, Marciani Magno S, Dell’Acqua F, Vedaldi D: Studies on the mechanism of action of mitomycin C. Farmaco Sci. 1978 Sep;33(9):651-66. Pubmed
  4. Verweij J, Pinedo HM: Mitomycin C: mechanism of action, usefulness and limitations. Anticancer Drugs. 1990 Oct;1(1):5-13. Pubmed
Enzymes

1. NADPH--cytochrome P450 reductase

Actions: substrate

This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5

UniProt ID: P16435 Link_out
Gene: POR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bligh HF, Bartoszek A, Robson CN, Hickson ID, Kasper CB, Beggs JD, Wolf CR: Activation of mitomycin C by NADPH:cytochrome P-450 reductase. Cancer Res. 1990 Dec 15;50(24):7789-92. Pubmed
  2. Vromans RM, van de Straat R, Groeneveld M, Vermeulen NP: One-electron reduction of mitomycin c by rat liver: role of cytochrome P-450 and NADPH-cytochrome P-450 reductase. Xenobiotica. 1990 Sep;20(9):967-78. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19