Mitomycin
Identification
- Name
- Mitomycin
- Accession Number
- DB00305
- Description
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
Structure for Mitomycin (DB00305)
- 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
- Associated Conditions
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- 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.
Target Actions Organism ADNA cross-linking/alkylationHumans - 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
Learn about our commercial Adverse Effects data.
Learn More- 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
- 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.
Drug Interaction Unlock Additional DataAbatacept The risk or severity of adverse effects can be increased when Mitomycin is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Mitomycin. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Mitomycin. Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Mitomycin. Acetylsalicylic acid The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Mitomycin. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Mitomycin. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Mitomycin. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Mitomycin. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Mitomycin. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Mitomycin. Additional Data Available- Extended DescriptionExtended DescriptionAvailable for Purchase
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - SeveritySeverityAvailable for Purchase
A severity rating for each drug interaction, from minor to major.
Learn more - Evidence LevelEvidence LevelAvailable for Purchase
A rating for the strength of the evidence supporting each drug interaction.
Learn more - ActionActionAvailable for Purchase
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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- Food Interactions
- No interactions found.
Products
- International/Other Brands
- Mitozytrex
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataJelmyto 40 mg/1 Ureteral UroGen Pharma, Inc. 2020-05-01 Not applicable US 
Mitomycin for Injection Powder, for solution Intravenous; Intravesical TEVA Canada Limited 1997-10-22 2017-02-10 Canada 
Mitomycin for Injection Powder, for solution Intravenous; Intravesical TEVA Canada Limited 1997-10-22 Not applicable Canada Mitomycin for Injection USP Powder, for solution Intravenous; Intravesical Pfizer Canada Ulc 1998-03-12 2020-02-28 Canada Mitomycin for Injection USP Powder, for solution Intravenous; Intravesical Accord Healthcare Inc 2018-04-30 Not applicable Canada Mitomycin for Injection USP Powder, for solution Intravenous; Intravesical Pfizer Canada Ulc 1998-07-15 2020-02-28 Canada Mitosol Kit 0.2 mg/1mL Ophthalmic Mobius Therapeutics LLC 2012-02-08 Not applicable US Mutamycin Inj 20mg/vial Powder, for solution Intravenous; Intravesical Bristol Myers Squibb 1984-12-31 2006-05-29 Canada Mutamycin Inj 5mg/vial Powder, for solution Intravenous; Intravesical Bristol Myers Squibb 1977-12-31 2006-05-29 Canada Additional Data Available- Application NumberApplication NumberAvailable for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct CodeAvailable for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataMitomycin Injection, powder, lyophilized, for solution 20 mg/40mL Intravenous Bedford Pharmaceuticals 1996-05-01 2013-01-31 US Mitomycin Injection, powder, lyophilized, for solution 20 mg/40mL Intravenous Mylan Institutional LLC 2020-08-28 Not applicable US Mitomycin Injection, powder, lyophilized, for solution 40 mg/80mL Intravenous West-Ward Pharmaceuticals Corp 1999-09-01 Not applicable US Mitomycin Injection, powder, lyophilized, for solution 0.5 mg/1mL Intravenous Bedford Pharmaceuticals 2001-09-28 2013-01-31 US Mitomycin Injection, powder, lyophilized, for solution 20 mg/40mL Intravenous Mylan Institutional LLC 2018-02-28 Not applicable US Mitomycin Injection, powder, lyophilized, for solution 5 mg/10mL Intravenous Accord Healthcare Inc 2009-06-18 Not applicable US Mitomycin Injection, powder, lyophilized, for solution 40 mg/10mL Intravenous Accord Healthcare Inc 2013-05-03 Not applicable US Mitomycin Injection, powder, lyophilized, for solution 20 mg/40mL Intravenous BluePoint Laboratories 2019-05-14 Not applicable US Mitomycin Injection, powder, lyophilized, for solution 5 mg/10mL Intravenous Bedford Pharmaceuticals 1996-05-01 2013-01-31 US Mitomycin Injection, powder, lyophilized, for solution 20 mg/40mL Intravenous West-Ward Pharmaceuticals Corp 1996-05-01 Not applicable US Additional Data Available- Application NumberApplication NumberAvailable for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct CodeAvailable for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories
- ATC Codes
- L01DC03 — Mitomycin
- Drug Categories
- Alkylating Activity
- Alkylating Drugs
- Antibiotics, Antineoplastic
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Azirines
- Cardiotoxic antineoplastic agents
- Compounds used in a research, industrial, or household setting
- Cross-Linking Reagents
- Cytotoxic Antibiotics and Related Substances
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Immunosuppressive Agents
- Indicators and Reagents
- Indolequinones
- Indoles
- Mitomycins
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Noxae
- Nucleic Acid Synthesis Inhibitors
- Toxic Actions
- 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)
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
- 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. [PubMed:9383461]
- FDA Approved Drug Products: Jelmyto (mitomycin) pyelocalyceal solution [Link]
- External Links
- Human Metabolome Database
- HMDB0014450
- KEGG Drug
- D00208
- KEGG Compound
- C06681
- PubChem Compound
- 5746
- PubChem Substance
- 46508353
- ChemSpider
- 5544
- BindingDB
- 50428658
- 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
- AHFS Codes
- 10:00.00 — Antineoplastic Agents
- FDA label
- Download (82.3 KB)
- MSDS
- Download (77.9 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Cancer, Bladder 1 4 Completed Prevention Glaucoma 1 4 Completed Prevention High Myopia 1 4 Completed Treatment Conjunctival Intraepithelial Neoplasia / Corneal Intraepithelial Neoplasia 1 4 Completed Treatment Disorders, Refractive 1 4 Completed Treatment Glaucoma 1 4 Completed Treatment Open Angle Glaucoma (OAG) / Open-angle Glaucoma (OAG) 2 4 Not Yet Recruiting Treatment Cancer, Bladder 1 4 Recruiting Prevention Presbyopia 2 4 Recruiting Treatment Glaucoma / Glaucoma Open-Angle Primary / Open Angle Glaucoma (OAG) / 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
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 20 mg Injection, powder, lyophilized, for solution Parenteral 5 mg Powder, for solution Intravesical 20 MG Injection, solution 28.6 mg/100mL Injection, powder, for solution Intravenous 20 mg Injection, powder, for solution Parenteral 20 MG Injection, powder, for solution 40 MG Injection, powder, lyophilized, for solution Parenteral 20 mg Injection, powder, for solution Intravesical; Parenteral 1 MG/ML Injection, powder, for solution Intravesical 20 mg/vial Powder, for solution Intravesical 20 mg/vial Injection, powder, lyophilized, for solution Intravenous 0.5 mg/1mL Injection, powder, lyophilized, for solution Intravenous 20 mg/10mL Injection, powder, lyophilized, for solution Intravenous 20 mg/40mL Injection, powder, lyophilized, for solution Intravenous 40 mg/80mL Injection, powder, lyophilized, for solution Intravenous 40 mg/10mL Injection, powder, lyophilized, for solution Intravenous 5 mg/10mL Solution / drops Ophthalmic 20 mg/100mL Injection, powder, for solution Intravesical 10 mg Injection, powder, for solution Intravesical 2 mg Injection, powder, for solution Intravesical 20 mg Powder, for solution Intravesical; Parenteral 40 MG Injection, powder, for solution Parenteral 10 mg Injection, powder, for solution Parenteral 2 mg Solution / drops Auricular (otic); Ophthalmic 20 mg/100mL Powder, for solution Intravenous; Intravesical Injection, powder, for solution Parenteral 1 mg/ml Injection, powder, for solution Intravesical 40 mg Injection, solution 20 mg/100mL Injection, solution 40 mg/100mL Injection, powder, for solution 10 mg Injection, powder, for solution 2 mg Injection, powder, for solution 20 mg Injection Intravenous 10 mg Injection Intravenous 2 mg Injection Intravenous 20 mg Kit Ophthalmic 0.2 mg/1mL Powder, for solution Intravesical 40 MG Injection, powder, lyophilized, for solution Intravenous 5 mg Injection, powder, for solution Intravenous 20 mg/40mL Injection, powder, for solution Intravenous 40 mg/80mL Injection, powder, for solution Intravenous 5 mg/10mL - Prices
Unit description Cost Unit Mutamycin 40 mg vial 878.48USD vial Mutamycin 20 mg vial 434.8USD vial Mitomycin 40 mg vial 300.0USD vial Mitomycin 20 mg vial 142.55USD vial Mutamycin 5 mg vial 128.75USD vial Mitomycin 5 mg vial 52.43USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region Unlock Additional DataUS8186511 No 2012-05-29 2026-07-19 US US9205075 No 2015-12-08 2026-07-19 US US7806265 No 2010-10-05 2029-02-01 US US9649428 No 2017-05-16 2029-05-21 US US9539241 No 2017-01-10 2028-01-02 US US9040074 No 2011-01-20 2031-01-20 US US9950069 No 2011-01-20 2031-01-20 US Additional Data Available- Filed OnFiled OnAvailable for Purchase
The date on which a patent was filed with the relevant government.
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Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) >360 °C PhysProp boiling point (°C) 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 10.1 mg/mL ALOGPS logP -0.55 ALOGPS logP -1 ChemAxon logS -1.5 ALOGPS pKa (Strongest Acidic) 14.97 ChemAxon pKa (Strongest Basic) 5.76 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 146.89 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 83.27 m3·mol-1 ChemAxon Polarizability 32.77 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - 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 inhibitor Non-inhibitor 0.7642 CYP450 2D6 inhibitor Non-inhibitor 0.7464 CYP450 2C19 inhibitor Non-inhibitor 0.6115 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
Yes
Cross-linking/alkylation
References
- 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]
- Verweij J, Pinedo HM: Mitomycin C: mechanism of action, usefulness and limitations. Anticancer Drugs. 1990 Oct;1(1):5-13. [PubMed:2131038]
- 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
- 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]
- 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]
Drug created on June 13, 2005 07:24 / Updated on January 25, 2021 22:38