- Accession Number
- DB00305 (APRD00284)
- Small Molecule
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]
- Mitomycin C
- External IDs
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Mitomycin for Injection Powder, for solution 20 mg Intravenous; Intravesical Teva 1997-10-22 Not applicable Mitomycin for Injection Powder, for solution 5 mg Intravenous; Intravesical Teva 1997-10-22 2017-02-10 Mitomycin for Injection USP Powder, for solution 5 mg Intravenous; Intravesical Hospira, Inc. 1998-07-15 Not applicable Mitomycin for Injection USP Powder, for solution 20 mg Intravenous; Intravesical Accord Healthcare Limited Not applicable Not applicable Mitomycin for Injection USP Powder, for solution 20 mg Intravenous; Intravesical Hospira, Inc. 1998-03-12 Not applicable Mitosol Kit 0.2 mg/1mL Mobius Therapeutics LLC 2012-02-08 Not applicable Mutamycin Inj 20mg/vial Powder, for solution 20 mg Intravenous; Intravesical Bristol Myers Squibb 1984-12-31 2006-05-29 Mutamycin Inj 5mg/vial Powder, for solution 0.5 mg Intravenous; Intravesical Bristol Myers Squibb 1977-12-31 2006-05-29
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Mitomycin Injection, powder, lyophilized, for solution 20 mg/40mL Intravenous West-Ward Pharmaceuticals Corp 1996-05-01 Not applicable Mitomycin Injection, powder, lyophilized, for solution 40 mg/80mL Intravenous Accord Healthcare Limited 2011-03-11 Not applicable Mitomycin Injection, powder, lyophilized, for solution 0.5 mg/1mL Intravenous Bedford Pharmaceuticals 2001-09-28 2012-11-30 Mitomycin Injection, powder, lyophilized, for solution 0.5 mg/1mL Intravenous Bedford Pharmaceuticals 2001-10-11 2012-10-31 Mitomycin Injection, powder, lyophilized, for solution 40 mg/80mL Intravenous Mylan Institutional LLC 2018-02-28 Not applicable Mitomycin Injection, powder, lyophilized, for solution 5 mg/10mL Intravenous Accord Healthcare Limited 2009-06-18 Not applicable Mitomycin Injection, powder, lyophilized, for solution 20 mg/40mL Intravenous Bedford Pharmaceuticals 1996-05-01 2013-01-31 Mitomycin Injection, powder, lyophilized, for solution 20 mg/10mL Intravenous Accord Healthcare Limited 2013-05-03 Not applicable Mitomycin Injection, powder, lyophilized, for solution 5 mg/10mL Intravenous Mylan Institutional LLC 2018-02-28 Not applicable Mitomycin Injection, powder, lyophilized, for solution 40 mg/80mL Intravenous West-Ward Pharmaceuticals Corp 1999-09-01 Not applicable
- International/Other Brands
- Mitozytrex / Mutamycin
- Alkylating Activity
- Alkylating Drugs
- Antibiotics, Antineoplastic
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cardiotoxic antineoplastic agents
- Cross-Linking Reagents
- Cytotoxic Antibiotics and Related Substances
- Enzyme Inhibitors
- Immunosuppressive Agents
- Indicators and Reagents
- Laboratory Chemicals
- Myelosuppressive Agents
- Nucleic Acid Synthesis Inhibitors
- P-glycoprotein/ABCB1 Substrates
- Toxic Actions
- CAS number
- Average: 334.3272
- Chemical Formula
- InChI Key
- IUPAC Name
- [(4S,6S,7R,8S)-11-amino-7-methoxy-12-methyl-10,13-dioxo-2,5-diazatetracyclo[22.214.171.124²,⁷.0⁴,⁶]trideca-1(9),11-dien-8-yl]methyl carbamate
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.
- Associated Conditions
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 ADNAantagonistcross-linking/alkylation Human
- Volume of distribution
- Not Available
- Protein binding
- Not Available
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
- Not Available
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
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction (R)-warfarin The risk or severity of bleeding can be increased when (R)-warfarin is combined with Mitomycin. (S)-Warfarin The risk or severity of bleeding can be increased when (S)-Warfarin is combined with Mitomycin. 2-Methoxyethanol The risk or severity of adverse effects can be increased when Mitomycin is combined with 2-Methoxyethanol. 4-hydroxycoumarin The risk or severity of bleeding can be increased when 4-hydroxycoumarin is combined with Mitomycin. 9-(N-methyl-L-isoleucine)-cyclosporin A The risk or severity of adverse effects can be increased when Mitomycin is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A. Abatacept 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. Abemaciclib The serum concentration of Mitomycin can be increased when it is combined with Abemaciclib. Abetimus The risk or severity of adverse effects can be increased when Mitomycin is combined with Abetimus. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Mitomycin.
- Food Interactions
- Not Available
- Synthesis Reference
Leslie Jimenez, Zheng Wang, "Synthesis of mitomycin and its analogs." U.S. Patent US5523411, issued June, 1972.US5523411
- General References
- Not Available
- External Links
- ATC Codes
- L01DC03 — Mitomycin
- AHFS Codes
- 10:00.00 — Antineoplastic Agents
- FDA label
- Download (82.3 KB)
- Download (77.9 KB)
- Clinical Trials
- 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
- 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 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 Powder, for solution Intravenous; Intravesical 20 mg Powder, for solution Intravenous; Intravesical 5 mg Kit 0.2 mg/1mL 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
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 vialDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patent Number Pediatric Extension Approved Expires (estimated) US8186511 No 2012-05-29 2026-07-19 US9205075 No 2015-12-08 2026-07-19 US7806265 No 2010-10-05 2029-02-01 US9649428 No 2017-05-16 2029-05-21 US9539241 No 2017-01-10 2028-01-02
- 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 -3 ChemAxon logS -1.5 ALOGPS pKa (Strongest Acidic) -0.3 ChemAxon pKa (Strongest Basic) 6.8 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
- Mass Spec (NIST)
- Not Available
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
- 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.
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Indoles and derivatives
- Sub Class
- Direct Parent
- Alternative Parents
- Indoles / Quinones / Pyrrolizines / Piperazines / Vinylogous amides / Pyrrolines / Pyrrolidines / Azacyclic compounds / Aziridines / Carboximidic acids and derivativesDialkylamines / Enamines / Hydrocarbon derivatives / Imines / Organopnictogen compounds / Monoalkylamines / Organic oxides show 7 more
- Mitomycin / Indole / Quinone / Pyrrolizine / 1,4-diazinane / Piperazine / Pyrrolidine / Vinylogous amide / Pyrroline / KetoneAziridine / Carboximidic acid derivative / Secondary aliphatic amine / Enamine / Azacycle / Secondary amine / Primary aliphatic amine / Organic oxide / Organopnictogen compound / Organic oxygen compound / Imine / Carbonyl group / Organic nitrogen compound / Organonitrogen compound / Organooxygen compound / Hydrocarbon derivative / Primary amine / Amine / Aliphatic heteropolycyclic compound show 19 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- mitomycin (CHEBI:27504) / Quinones (C06681)
- 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
- 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]
- 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]
- 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]
- Pharmacological action
- 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
- Uniprot ID
- Uniprot Name
- NADPH--cytochrome P450 reductase
- Molecular Weight
- 76689.12 Da
- 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 December 14, 2018 17:05