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Identification
NameMitomycin
Accession NumberDB00305  (APRD00284)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
7-Amino-9alpha-methoxymitosaneNot AvailableNot Available
AmetycineNot AvailableNot Available
MitamycinNot AvailableNot Available
Mitocin-CNot AvailableNot Available
Mitomycin CNot AvailableNot Available
MMCNot AvailableNot Available
MutamycinNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
MitosolMobius Therapeutics, LLC
MitozytrexNot Available
Brand mixturesNot Available
Categories
CAS number50-07-7
WeightAverage: 334.3272
Monoisotopic: 334.127719706
Chemical FormulaC15H18N4O5
InChI KeyNWIBSHFKIJFRCO-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIndoles and Derivatives
SubclassIndolequinones
Direct parentMitomycins
Alternative parentsIndoles; p-Benzoquinones; p-Quinones; Pyrrolizines; Piperazines; Diazinanes; Pyrrolines; Pyrrolidines; Tertiary Amines; Carbamic Acids and Derivatives; Ethers; Enamines; Dialkylamines; Polyamines; Aziridines
Substituentsindole; p-benzoquinone; quinone; p-quinone; pyrrolizine; piperazine; 1,4-diazinane; pyrroline; pyrrolidine; tertiary amine; carbamic acid derivative; ketone; secondary amine; secondary aliphatic amine; polyamine; aziridine; enamine; ether; carbonyl group; organonitrogen compound; amine
Classification descriptionThis compound belongs to the mitomycins. These are polycyclic compounds whose structure is based on an aziridine ring linked to a 7-amino-6-methyl-cyclohexa[b]pyrrolizine-5,8-dione.
Pharmacology
IndicationFor 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.
PharmacodynamicsMitomycin 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 actionMitomycin 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.
AbsorptionErratic.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Primarily hepatic, some in various other tissues.

Route of eliminationApproximately 10% of a dose of mitomycin is excreted unchanged in the urine.
Half life8-48 min
ClearanceNot Available
ToxicityOral, mouse: LD50 = 23 mg/kg; Oral, rat: LD50 = 30 mg/kg. Symptoms of overdose include nausea and vomiting.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9154
Blood Brain Barrier - 0.9659
Caco-2 permeable - 0.6572
P-glycoprotein substrate Substrate 0.7861
P-glycoprotein inhibitor I Non-inhibitor 0.7231
P-glycoprotein inhibitor II Non-inhibitor 0.5469
Renal organic cation transporter Non-inhibitor 0.8032
CYP450 2C9 substrate Non-substrate 0.8997
CYP450 2D6 substrate Non-substrate 0.8332
CYP450 3A4 substrate Substrate 0.6879
CYP450 1A2 substrate Non-inhibitor 0.5813
CYP450 2C9 substrate Non-inhibitor 0.7642
CYP450 2D6 substrate Non-inhibitor 0.7464
CYP450 2C19 substrate Non-inhibitor 0.6115
CYP450 3A4 substrate Non-inhibitor 0.8308
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5204
Ames test AMES toxic 0.9107
Carcinogenicity Non-carcinogens 0.9263
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 4.0153 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9788
hERG inhibition (predictor II) Non-inhibitor 0.7214
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
FormRouteStrength
Injection, powder, lyophilized, for solutionTopical0.2 mg/mL
Powder, for solutionIntravesical
Prices
Unit descriptionCostUnit
Mutamycin 40 mg vial878.48USDvial
Mutamycin 20 mg vial434.8USDvial
Mitomycin 40 mg vial300.0USDvial
Mitomycin 20 mg vial142.55USDvial
Mutamycin 5 mg vial128.75USDvial
Mitomycin 5 mg vial52.43USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point>360 °CPhysProp
boiling point534 °CPhysProp
water solubilitySoluble (8430 mg/L)Not Available
logP-0.40HANSCH,C ET AL. (1995)
pKa10.9HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility1.01e+01 g/lALOGPS
logP-0.55ALOGPS
logP-3ChemAxon
logS-1.5ALOGPS
pKa (strongest acidic)-0.3ChemAxon
pKa (strongest basic)6.8ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count7ChemAxon
hydrogen donor count3ChemAxon
polar surface area146.89ChemAxon
rotatable bond count4ChemAxon
refractivity83.27ChemAxon
polarizability32.77ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Leslie Jimenez, Zheng Wang, “Synthesis of mitomycin and its analogs.” U.S. Patent US5523411, issued June, 1972.

US5523411
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00208
KEGG CompoundC06681
PubChem Compound5746
PubChem Substance46508353
ChemSpider5544
ChEBI27504
ChEMBLCHEMBL105
Therapeutic Targets DatabaseDAP001402
PharmGKBPA450524
Drug Product Database2230729
RxListhttp://www.rxlist.com/cgi/generic3/mitomycin.htm
Drugs.comhttp://www.drugs.com/cdi/mitomycin.html
WikipediaMitomycin
ATC CodesL01DC03
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelshow(82.3 KB)
MSDSshow(77.9 KB)
Interactions
Drug Interactions
Drug
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
VinblastinePotentially severe lung toxicity
VincristinePotentially severe lung toxicity
VindesinePotentially severe lung toxicity
Food InteractionsNot Available

Targets

1. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: antagonist cross-linking/alkylation

Components

Name UniProt ID Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
NADPH--cytochrome P450 reductase P16435 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09