You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
7-Amino-9alpha-methoxymitosane
Ametycine
Mitamycin
Mitocin-C
Mitomycin
Mitomycin C
MMC
Mutamycin
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mitomycin for Injectionpowder for solution20 mgintravenous; intravesicalTeva Canada Limited1997-10-22Not applicableCanada
Mitomycin for Injectionpowder for solution5 mgintravenous; intravesicalTeva Canada Limited1997-10-22Not applicableCanada
Mitomycin for Injection USPpowder for solution5 mgintravenous; intravesicalHospira Healthcare Corporation1998-07-15Not applicableCanada
Mitomycin for Injection USPpowder for solution20 mgintravenous; intravesicalHospira Healthcare Corporation1998-03-12Not applicableCanada
MitosolkitureteralMobius Therapeutics LLC2012-02-08Not applicableUs
Mutamycin Inj 20mg/vialpowder for solution20 mgintravenous; intravesicalBristol Myers Squibb Canada1984-12-312006-05-29Canada
Mutamycin Inj 5mg/vialpowder for solution0.5 mgintravenous; intravesicalBristol Myers Squibb Canada1977-12-312006-05-29Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mitomycininjection, powder, lyophilized, for solution20 mg/40mLintravenousAccord Healthcare Inc2009-06-10Not applicableUs
Mitomycininjection, powder, lyophilized, for solution40 mg/10mLintravenousAccord Healthcare Inc2013-05-03Not applicableUs
Mitomycininjection, powder, lyophilized, for solution20 mg/10mLintravenousAccord Healthcare Inc2013-05-03Not applicableUs
Mitomycininjection, powder, lyophilized, for solution5 mg/10mLintravenousAccord Healthcare Inc2013-05-03Not applicableUs
Mitomycininjection, powder, lyophilized, for solution40 mg/80mLintravenousAccord Healthcare Inc2011-03-11Not applicableUs
Mitomycininjection, powder, lyophilized, for solution5 mg/10mLintravenousAccord Healthcare Inc2009-06-18Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
MitozytrexNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII50SG953SK6
CAS number50-07-7
WeightAverage: 334.3272
Monoisotopic: 334.127719706
Chemical FormulaC15H18N4O5
InChI KeyInChIKey=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
IUPAC Name
[(4S,6S,7R,8S)-11-amino-7-methoxy-12-methyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.0²,⁷.0⁴,⁶]trideca-1(9),11-dien-8-yl]methyl carbamate
SMILES
CO[C@]12[[email protected]]3N[[email protected]]3CN1C1=C([[email protected]]2COC(N)=O)C(=O)C(N)=C(C)C1=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as mitomycins. These are polycyclic compounds with a structure based on an aziridine ring linked to a 7-amino-6-methyl-cyclohexa[b]pyrrolizine-5,8-dione.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassIndolequinones
Direct ParentMitomycins
Alternative Parents
Substituents
  • Mitomycin
  • Indole
  • Quinone
  • Pyrrolizine
  • Piperazine
  • 1,4-diazinane
  • Vinylogous amide
  • Pyrroline
  • Pyrrolidine
  • Tertiary amine
  • Ketone
  • Azacycle
  • Secondary amine
  • Enamine
  • Secondary aliphatic amine
  • Aziridine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.9154
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6572
P-glycoprotein substrateSubstrate0.7861
P-glycoprotein inhibitor INon-inhibitor0.7231
P-glycoprotein inhibitor IINon-inhibitor0.5469
Renal organic cation transporterNon-inhibitor0.8032
CYP450 2C9 substrateNon-substrate0.8997
CYP450 2D6 substrateNon-substrate0.8332
CYP450 3A4 substrateSubstrate0.6879
CYP450 1A2 substrateNon-inhibitor0.5813
CYP450 2C9 inhibitorNon-inhibitor0.7642
CYP450 2D6 inhibitorNon-inhibitor0.7464
CYP450 2C19 inhibitorNon-inhibitor0.6115
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5204
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.9263
BiodegradationNot ready biodegradable1.0
Rat acute toxicity4.0153 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9788
hERG inhibition (predictor II)Non-inhibitor0.7214
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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 solutionintravenous20 mg/40mL
Injection, powder, lyophilized, for solutionintravenous20 mg/10mL
Injection, powder, lyophilized, for solutionintravenous40 mg/80mL
Injection, powder, lyophilized, for solutionintravenous40 mg/10mL
Injection, powder, lyophilized, for solutionintravenous5 mg/10mL
Powder for solutionintravenous; intravesical20 mg
Powder for solutionintravenous; intravesical5 mg
Kitureteral
Powder for solutionintravenous; intravesical0.5 mg
Prices
Unit descriptionCostUnit
Mutamycin 40 mg vial878.48USD vial
Mutamycin 20 mg vial434.8USD vial
Mitomycin 40 mg vial300.0USD vial
Mitomycin 20 mg vial142.55USD vial
Mutamycin 5 mg vial128.75USD vial
Mitomycin 5 mg vial52.43USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7806265 No2009-02-012029-02-01Us
US8186511 No2006-07-192026-07-19Us
US9205075 No2006-07-192026-07-19Us
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 Solubility10.1 mg/mLALOGPS
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 Area146.89 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity83.27 m3·mol-1ChemAxon
Polarizability32.77 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

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

US5523411
General ReferencesNot Available
External Links
ATC CodesL01DC03
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (82.3 KB)
MSDSDownload (77.9 KB)
Interactions
Drug Interactions
Drug
ClozapineThe risk or severity of adverse effects can be increased when Mitomycin is combined with Clozapine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Mitomycin.
LeflunomideThe risk or severity of adverse effects can be increased when Mitomycin is combined with Leflunomide.
LumacaftorThe serum concentration of Mitomycin can be decreased when it is combined with Lumacaftor.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Mitomycin.
NatalizumabThe risk or severity of adverse effects can be increased when Mitomycin is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Mitomycin.
RanolazineThe serum concentration of Mitomycin can be increased when it is combined with Ranolazine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Mitomycin.
SaquinavirThe serum concentration of Mitomycin can be increased when it is combined with Saquinavir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Mitomycin.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Mitomycin.
TesmilifeneThe serum concentration of Mitomycin can be decreased when it is combined with Tesmilifene.
TofacitinibMitomycin may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Mitomycin.
VerapamilThe serum concentration of Mitomycin can be increased when it is combined with Verapamil.
VinblastineThe risk or severity of adverse effects can be increased when Vinblastine is combined with Mitomycin.
VincristineThe risk or severity of adverse effects can be increased when Vincristine is combined with Mitomycin.
VindesineThe risk or severity of adverse effects can be increased when Vindesine is combined with Mitomycin.
VinorelbineThe risk or severity of adverse effects can be increased when Vinorelbine is combined with Mitomycin.
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
antagonistcross-linking/alkylation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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:17139284 ]
  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:17016423 ]
  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:744262 ]
  4. Verweij J, Pinedo HM: Mitomycin C: mechanism of action, usefulness and limitations. Anticancer Drugs. 1990 Oct;1(1):5-13. [PubMed:2131038 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function:
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.
Gene Name:
POR
Uniprot ID:
P16435
Molecular Weight:
76689.12 Da
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:2123741 ]
  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:2122607 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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:14985103 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on July 24, 2016 01:52