Identification

Summary

Mitomycin is an antimetabolite used as an adjunct to ab externo (outside approach) eye surgeries for the treatment of glaucoma and used as a chemotherapeutic agent for various malignancies.

Brand Names
Jelmyto, Mitosol, Mutamycin
Generic Name
Mitomycin
DrugBank Accession Number
DB00305
Background

Mitomycin is an antineoplastic antibiotic first isolated by Japanese microbiologists in the 1950s from cultures of Streptomyces caespitosus.2,1 It is an alkylating agent that inhibits DNA synthesis (and, at higher concentrations, RNA and protein synthesis) by cross-linking the complementary strands of the DNA double helix.1 Few other antibiotics have been discovered that work via this alkylating mechanism, making mitomycin relatively unique in the space of microbiota-derived therapies.1

Mitomycin's cross-linking activity has resulted in its approval for the treatment of a variety of cancers - the most recent of which is an April 2020 approval for its use in low-grade Upper Tract Urothelial Cancer (LG-UTUC)2 - as well as adjunctly to ab externo glaucoma surgeries.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 334.3272
Monoisotopic: 334.127719706
Chemical Formula
C15H18N4O5
Synonyms
  • 7-Amino-9alpha-methoxymitosane
  • Ametycine
  • Mitamycin
  • Mitocin-C
  • Mitomycin
  • Mitomycin C
  • MMC
External IDs
  • NSC-26980

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. Mitomycin is also indicated as a pyelocalyceal solution for the treatment of adults with low-grade upper tract urothelial cancer (LG-UTUC).2

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
ADNA
cross-linking/alkylation
Humans
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

Adverse Effects
Adverseeffects
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Toxicity

Oral, mouse: LD50 = 23 mg/kg; Oral, rat: LD50 = 30 mg/kg. Symptoms of overdose include nausea and vomiting.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Mitomycin is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Mitomycin.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Mitomycin.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Mitomycin.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Mitomycin.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Mitomycin.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Mitomycin.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Mitomycin.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Mitomycin.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Mitomycin.
Interactions
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Food Interactions
No interactions found.

Products

Products2
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International/Other Brands
Mitozytrex
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Jelmyto40 mg/1UreteralUroGen Pharma, Inc.2020-05-01Not applicableUS flag
Mitomycin for InjectionPowder, for solution5 mg / vialIntravenous; IntravesicalTEVA Canada Limited1997-10-222017-02-10Canada flag
Mitomycin for InjectionPowder, for solution20 mg / vialIntravenous; IntravesicalTEVA Canada Limited1997-10-22Not applicableCanada flag
Mitomycin for Injection USPPowder, for solution5 mg / vialIntravenous; IntravesicalPfizer Canada Ulc1998-07-152020-02-28Canada flag
Mitomycin for Injection USPPowder, for solution20 mg / vialIntravenous; IntravesicalPfizer Canada Ulc1998-03-122020-02-28Canada flag
Mitomycin for Injection USPPowder, for solution20 mg / vialIntravenous; IntravesicalAccord Healthcare Inc2018-04-30Not applicableCanada flag
MitosolKit0.2 mg/1mLOphthalmicMobius Therapeutics LLC2012-02-08Not applicableUS flag
Mutamycin Inj 20mg/vialPowder, for solution20 mg / vialIntravenous; IntravesicalBristol Myers Squibb1984-12-312006-05-29Canada flag
Mutamycin Inj 5mg/vialPowder, for solution0.5 mg / mLIntravenous; IntravesicalBristol Myers Squibb1977-12-312006-05-29Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MitomycinInjection, powder, lyophilized, for solution40 mg/80mLIntravenousWest-Ward Pharmaceuticals Corp1999-09-01Not applicableUS flag
MitomycinInjection, powder, lyophilized, for solution40 mg/10mLIntravenousAccord Healthcare Inc2013-05-03Not applicableUS flag
MitomycinInjection, powder, lyophilized, for solution0.5 mg/1mLIntravenousBedford Pharmaceuticals2001-09-282012-11-30US flag
MitomycinInjection, powder, lyophilized, for solution5 mg/10mLIntravenousMylan Institutional LLC2017-10-13Not applicableUS flag
MitomycinInjection, powder, lyophilized, for solution40 mg/80mLIntravenousBedford Pharmaceuticals1999-09-012012-11-30US flag
MitomycinInjection, powder, lyophilized, for solution20 mg/40mLIntravenousMylan Institutional LLC2018-02-28Not applicableUS flag
MitomycinInjection, powder, lyophilized, for solution20 mg/40mLIntravenousBluePoint Laboratories2019-05-14Not applicableUS flag
MitomycinInjection, powder, lyophilized, for solution20 mg/40mLIntravenousAccord Healthcare Inc2009-06-10Not applicableUS flag
MitomycinInjection, powder, lyophilized, for solution0.5 mg/1mLIntravenousBedford Pharmaceuticals2001-10-112012-10-31US flag
MitomycinInjection, powder, lyophilized, for solution40 mg/80mLIntravenousMylan Institutional LLC2020-08-28Not applicableUS flag

Categories

ATC Codes
L01DC03 — Mitomycin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolequinones
Direct Parent
Mitomycins
Alternative Parents
Indoles / Quinones / Pyrrolizines / Piperazines / Vinylogous amides / Pyrrolines / Pyrrolidines / Azacyclic compounds / Aziridines / Carboximidic acids and derivatives
show 7 more
Substituents
1,4-diazinane / Aliphatic heteropolycyclic compound / Amine / Azacycle / Aziridine / Carbonyl group / Carboximidic acid derivative / Enamine / Hydrocarbon derivative / Imine
show 19 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
mitomycin (CHEBI:27504) / Quinones (C06681)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
50SG953SK6
CAS number
50-07-7
InChI Key
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[7.4.0.0^{2,7}.0^{4,6}]trideca-1(9),11-dien-8-yl]methyl carbamate
SMILES
[H][C@]12CN3C4=C([C@@H](COC(N)=O)[C@@]3(OC)[C@@]1([H])N2)C(=O)C(N)=C(C)C4=O

References

Synthesis Reference

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

US5523411
General References
  1. Tomasz M: Mitomycin C: small, fast and deadly (but very selective). Chem Biol. 1995 Sep;2(9):575-9. doi: 10.1016/1074-5521(95)90120-5. [Article]
  2. FDA Approved Drug Products: Jelmyto (mitomycin) pyelocalyceal solution [Link]
Human Metabolome Database
HMDB0014450
KEGG Drug
D00208
KEGG Compound
C06681
PubChem Compound
5746
PubChem Substance
46508353
ChemSpider
5544
BindingDB
50428658
RxNav
632
ChEBI
27504
ChEMBL
CHEMBL105
ZINC
ZINC000030726187
Therapeutic Targets Database
DAP001402
PharmGKB
PA450524
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mitomycins
FDA label
Download (82.3 KB)
MSDS
Download (77.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentBladder Cancer, Cancer1
4CompletedPreventionGlaucoma1
4CompletedPreventionHigh Myopia1
4CompletedTreatmentConjunctival Intraepithelial Neoplasia / Corneal Intraepithelial Neoplasia1
4CompletedTreatmentDisorders, Refractive1
4CompletedTreatmentGlaucoma2
4CompletedTreatmentOpen Angle Glaucoma (OAG)2
4Not Yet RecruitingTreatmentBladder Cancer, Cancer1
4RecruitingPreventionPresbyopia2
4RecruitingTreatmentGlaucoma / Ocular Hypertension, Primary Open-angle Glaucoma (POAG) / Open Angle Glaucoma (OAG)1

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
  • Accord Healthcare
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bristol-Myers Squibb Co.
  • Hospira Inc.
  • Intas Pharmaceuticals Ltd.
  • Santec Chemicals Corp.
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous20 mg
Powder, for solutionIntravesical20 MG
Injection, powder, for solutionIntravenous20 mg
Injection, powder, for solutionParenteral10 MG
Injection, powder, for solutionParenteral20 MG
Injection, powder, for solution40 MG
Injection, powder, for solutionIntravesical; Parenteral1 MG/ML
Injection, powder, lyophilized, for solutionIntravenous0.5 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous20 mg/40mL
Injection, powder, lyophilized, for solutionIntravenous20 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous40 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous40 mg/80mL
Injection, powder, lyophilized, for solutionIntravenous5 mg/10mL
Injection, powder, for solutionIntravesical
InjectionIntravenous2 mg
InjectionIntravenous20 mg
Injection, powder, for solution10 MG
Powder, for solutionIntravesical; Parenteral40 MG
Injection, powder, for solutionParenteral
Powder, for solutionIntravenous; Intravesical20 mg / vial
Powder, for solutionIntravenous; Intravesical5 mg / vial
InjectionIntravenous
Injection, powder, for solutionIntra-arterial; Intravenous; Intravesical10 mg
Injection, powder, for solutionIntra-arterial; Intravenous; Intravesical2 mg
KitOphthalmic0.2 mg/1mL
Powder, for solutionIntravesical
Injection, powder, lyophilized, for solutionIntravenous5 mg
Injection, powder, for solutionIntravenous20 mg/40mL
Injection, powder, for solutionIntravenous40 mg/80mL
Injection, powder, for solutionIntravenous5 mg/10mL
Injection, powder, lyophilized, for solutionParenteral5 mg
Injection, powder, lyophilized, for solutionParenteral20 mg
Powder, for solutionIntravenous; Intravesical0.5 mg / mL
Powder2 mg/1vial
Powder10 mg/1vial
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)Region
US8186511No2012-05-292026-07-19US flag
US9205075No2015-12-082026-07-19US flag
US7806265No2010-10-052029-02-01US flag
US9649428No2017-05-162029-05-21US flag
US9539241No2017-01-102028-01-02US flag
US9040074No2015-05-262031-01-20US flag
US9950069No2018-04-242031-01-20US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)>360 °CPhysProp
boiling point (°C)534 °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-1ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)14.97ChemAxon
pKa (Strongest Basic)5.76ChemAxon
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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
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.
References
  1. 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. [Article]
  2. Verweij J, Pinedo HM: Mitomycin C: mechanism of action, usefulness and limitations. Anticancer Drugs. 1990 Oct;1(1):5-13. [Article]
  3. FDA Approved Drug Products: Jelmyto (mitomycin) pyelocalyceal solution [Link]

Enzymes

Kind
Protein
Organism
Humans
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
Uniprot Name
NADPH--cytochrome P450 reductase
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. [Article]
  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. [Article]

Drug created at June 13, 2005 13:24 / Updated at December 04, 2021 10:32