Mitomycin
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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
- Weight
- Average: 334.3272
Monoisotopic: 334.127719706 - Chemical Formula
- C15H18N4O5
- Synonyms
- 7-Amino-9alpha-methoxymitosane
- Ametycine
- Mitamycin
- Mitocin-C
- Mitomycin
- Mitomycin C
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Adenocarcinoma of the stomach •••••••••••• Used in combination to treat Anal cancer ••• ••••• Used in combination to treat Bladder cancer ••• ••••• Treatment of Breast cancer ••• ••••• Used in combination to treat Cervical cancer ••• ••••• - Contraindications & Blackbox Warnings
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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.
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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept 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. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Mitozytrex
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Jelmyto Kit; Powder, for solution 40 mg/1 Ureteral CENEXI - BLA 2020-05-01 Not applicable US Jelmyto Kit; Powder, for solution 40 mg/1 Ureteral UroGen Pharma, Inc. 2020-05-01 Not applicable US Mitomycin for Injection Powder, for solution 20 mg / vial Intravenous; Intravesical Teva Italia S.R.L. 1997-10-22 Not applicable Canada Mitomycin for Injection Powder, for solution 5 mg / vial Intravenous; Intravesical Teva Italia S.R.L. 1997-10-22 2017-02-10 Canada Mitomycin for Injection USP Powder, for solution 20 mg / vial Intravenous; Intravesical Accord Healthcare, S.L.U. 2018-04-30 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mitomycin Injection, powder, lyophilized, for solution 40 mg/80mL Intravenous Accord Healthcare, S.L.U. 2011-03-11 Not applicable US Mitomycin Injection, powder, lyophilized, for solution 5 mg/10mL Intravenous Sagent Pharmaceuticals 2023-06-15 Not applicable US Mitomycin Injection, powder, lyophilized, for solution 40 mg/80mL Intravenous BluePoint Laboratories 2019-05-14 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 Meitheal Pharmaceuticals Inc. 2022-09-08 Not applicable US
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)
- 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
- 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
- FDA label
- Download (82.3 KB)
- MSDS
- Download (77.9 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Available Not Available Renal Pelvis Urothelial Carcinoma / Ureter Urothelial Carcinoma / Urothelial Carcinoma / Urothelial Carcinoma of the Renal Pelvis and Ureter / Urothelial Carcinoma Recurrent / Urothelial Carcinoma Ureter Recurrent 1 somestatus stop reason just information to hide Not Available Completed Not Available Appendix Cancer / Cervical Cancer / Colorectal Cancer / Fallopian Tube Cancer / Gastric Cancer / Ovarian Cancer / Primary Peritoneal Carcinoma / Uterine Malignancies 1 somestatus stop reason just information to hide Not Available Completed Prevention Bladder Cancer 1 somestatus stop reason just information to hide Not Available Completed Prevention Myopia (Disorder) 1 somestatus stop reason just information to hide Not Available Completed Treatment Corneal Diseases 1 somestatus stop reason just information to hide
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 Kit; powder, for solution Ureteral 40 mg/1 Solution Intravenous 5.000 mg Injection, powder, lyophilized, for solution Parenteral 5 mg Powder, for solution Intravesical 20 MG Injection, powder, for solution Intravenous 20 mg Injection, powder, for solution Parenteral 10 MG Injection, powder, for solution Parenteral 20 MG Injection, powder, for solution Parenteral 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/1 Injection, powder, lyophilized, for solution Intravenous 20 mg/40mL Injection, powder, lyophilized, for solution Intravenous 40 mg/10mL Injection, powder, lyophilized, for solution Intravenous 40 mg/1 Injection, powder, lyophilized, for solution Intravenous 40 mg/80mL Injection, powder, lyophilized, for solution Intravenous 5 mg/10mL Injection, powder, for solution Intravesical Injection Intravenous 2 mg Injection Intravenous 20 mg Injection, powder, for solution 10 MG Powder, for solution Intravesical; Parenteral 40 MG Injection, powder, for solution Parenteral Powder, for solution Intravenous; Intravesical 20 mg / vial Powder, for solution Intravenous; Intravesical 5 mg / vial Injection, powder, for solution Parenteral 1 mg/ml Injection Intravenous 10 mg Injection Intravenous Injection, powder, for solution Intra-arterial; Intravenous; Intravesical 10 mg Injection, powder, for solution Intra-arterial; Intravenous; Intravesical 2 mg Powder Intravesical 10 mg Injection, powder, lyophilized, for solution; kit Ophthalmic 0.2 mg/1mL Powder, for solution 40 mg 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 Powder, for solution Intravenous; Intravesical 0.5 mg / mL Powder 2 mg/1vial Powder 10 mg/1vial - 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 US8186511 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 2015-05-26 2031-01-20 US US9950069 No 2018-04-24 2031-01-20 US
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 splash10-0k96-9032000000-addf881f05b59bd45e65 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0090000000-331ba3fb8b9c8810b9a1 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0091000000-124fd7070950fc983086 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-006x-0091000000-b99c00058ab0bc06ca8d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-1091000000-8db0d18ce26d81833601 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05mo-0091000000-0d5bdbd3c07eaf715cdb Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-002o-5093000000-1a108f59ff432aebf260 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 182.5802545 predictedDarkChem Lite v0.1.0 [M-H]- 183.6086545 predictedDarkChem Lite v0.1.0 [M-H]- 184.2574545 predictedDarkChem Lite v0.1.0 [M-H]- 180.13612 predictedDeepCCS 1.0 (2019) [M+H]+ 181.3066545 predictedDarkChem Lite v0.1.0 [M+H]+ 183.3336545 predictedDarkChem Lite v0.1.0 [M+H]+ 182.8993545 predictedDarkChem Lite v0.1.0 [M+H]+ 182.53168 predictedDeepCCS 1.0 (2019) [M+Na]+ 181.6149545 predictedDarkChem Lite v0.1.0 [M+Na]+ 184.0056545 predictedDarkChem Lite v0.1.0 [M+Na]+ 183.8819545 predictedDarkChem Lite v0.1.0 [M+Na]+ 188.44423 predictedDeepCCS 1.0 (2019)
Targets
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. [Article]
- Verweij J, Pinedo HM: Mitomycin C: mechanism of action, usefulness and limitations. Anticancer Drugs. 1990 Oct;1(1):5-13. [Article]
- FDA Approved Drug Products: Jelmyto (mitomycin) pyelocalyceal solution [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General 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
- Specific Function
- flavin adenine dinucleotide binding
- 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. [Article]
- 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 October 29, 2024 17:59