Coenzyme M
Identification
- Name
- Coenzyme M
- Accession Number
- DB09110
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
Coenzyme M (commonly known by it's salt form, Mesna) is a synthetic sulfhydryl (thiol) compound and is used for prophylaxis of Ifosfamide and cyclophosphamide induced hemorrhagic cystitis. [2]
- Structure
Structure for DB09110 (Coenzyme M)
- Synonyms
- 2-Mercaptoethane
- 2-Mercaptoethanesulfonate
- 2-mercaptoethanesulfonic acid
- 2-mercaptoethanesulphonic acid
- 2-mercaptoethylsulfonate
- 2-sulfanylethylsulfonate
- Coenzima M
- Coenzym M
- CoM
- HS-CoM
- reduced coenzyme M
- reduced CoM
- β-mercaptoethanesulfonic acid
- Product Ingredients
Ingredient UNII CAS InChI Key Mesna NR7O1405Q9 19767-45-4 XOGTZOOQQBDUSI-UHFFFAOYSA-M - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Mesna Injection, solution 100 mg/mL Intravenous Baxter Laboratories 1988-12-30 Not applicable US 
Mesna for Injection Solution 100 mg Intravenous; Oral Fresenius Kabi 2002-08-22 Not applicable Canada 
Mesnex Tablet, film coated 400 mg/1 Oral Baxter Laboratories 2002-03-21 Not applicable US Mesnex Injection, solution 100 mg/mL Intravenous Baxter Laboratories 1988-12-30 Not applicable US Uromitexan Solution 100 mg Intravenous Baxter Laboratories 2012-04-13 Not applicable Canada Uromitexan Solution 100 mg Intravenous; Oral Baxter Laboratories 2001-03-06 Not applicable Canada Uromitexan Inj 100mg/ml Liquid 100 mg Intravenous; Oral Bristol Labs Division Of Bristol Myers Squibb 1989-12-31 2001-06-12 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Mesna Injection, solution 100 mg/mL Intravenous Mylan Institutional 2012-04-03 2018-01-31 US Mesna Solution 100 mg/mL Intravenous Gland Pharma Limited 2017-12-20 Not applicable US Mesna Injection, solution 100 mg/mL Intravenous Fresenius Kabi 2001-09-05 Not applicable US Mesna Injection, solution 100 mg/mL Intravenous Alvogen, Inc. 2018-03-29 Not applicable US Mesna Injection, solution 100 mg/mL Intravenous Sagent Pharmaceuticals 2010-12-01 Not applicable US Mesna Injection, solution 100 mg/mL Intravenous AGILA SPECIALTIES PRIVATE LIMITED 2014-07-19 2017-09-28 US Mesna Injection, solution 100 mg/mL Intravenous Athenex Pharmaceutical Division, Llc. 2018-02-28 Not applicable US Mesna Injection, solution 100 mg/mL Intravenous Teva Parenteral Medicines, Inc. 2002-05-01 Not applicable US - International/Other Brands
- Mistabron / Mistabronco
- Categories
- UNII
- VHD28S0H7F
- CAS number
- 3375-50-6
- Weight
- Average: 142.197
Monoisotopic: 141.975835438 - Chemical Formula
- C2H6O3S2
- InChI Key
- ZNEWHQLOPFWXOF-UHFFFAOYSA-N
- InChI
- InChI=1S/C2H6O3S2/c3-7(4,5)2-1-6/h6H,1-2H2,(H,3,4,5)
- IUPAC Name
- 2-sulfanylethane-1-sulfonic acid
- SMILES
- OS(=O)(=O)CCS
Pharmacology
- Indication
Mesna is a uroprotective agent and is used prophylactically to reduce ifosfamide and cyclophosphamide induced hemorrhagic cystitis. (2)
- Associated Conditions
- Pharmacodynamics
Mesna binds to and inactivates acrolein there by preventing or reducing bladder problems
- Mechanism of action
A metabolite called acrolein is produced when ifosfamide and cyclophosphamide are metabolized. (1) This metabolite concentrates in the bladder and causes cell death via upregulation of reactive oxygen species (ROS), and activates inducible nitric oxide synthase (iNOS) which leads to production of nitric oxide (NO). (1) Both ROS and NO produce products which are detrimental to lipids, proteins and DNA strands. (1) Furthermore, ROS stimulate gene expression of pro-inflammatory cytokines such as TNF-α AND IL-1β. (1) Acrolein may also lead to ulceration of the bladder urothelium. (1) Mesna protects against cyclophosphamide and ifosfamide induced hemorrhagic cystitis by binding to their toxic metabolites. (1) Mesna is metabolized to dimesna and excreted by the kidneys. (1) Glutathione dihydrogenase acts on the reabsorbed portion and produces free sulfhydryl groups. (1) These free sulfhydryl groups bind acrolein in the bladder, allowing effective excretion and prevention of toxic effects. (1) In addition, Mesna binds to and detoxifies a urotoxic ifosfamide metabolite called 4-hydroxy-ifosfamide.
- Absorption
Peak plasma concentrations were reached within 1.5-4 hours for free mesna, and 3-7 hours for total mesna following oral administration. The average oral bioavailability is 58% for free mesna and 89% for total mesna. Food has no effect on the urinary availability of mesna.
- Volume of distribution
Vd = 0.652 ± 0.242 L/Kg after intravenous administration of mesna.
- Protein binding
Total plasma mesna is 28% protein bound. (3)
- Metabolism
Mesna undergoes rapid oxidation to mesna disulfide (dimesna) which is its major metabolite.
- Route of elimination
Within 24 hours, approximately 32% of administered dose is eliminated in the urine as mesna while 33% is eliminated as dimesna.
- Half life
The elimination half-life is 0.36 hours for mesna and 1.17 hours for dimesna.
- Clearance
Plasma clearance of mesna = 1.23 L/h/kg
- Toxicity
The following adverse events were most common (>10%) when mesna was administered with ifosfamide: nausea, vomiting, fatigue, fever, abdominal pain, constipation, diarrhea, leukopenia, anorexia, thrombocytopenia, anemia, granulocytopenia, asthenia, headache, alopecia, and somnolence. Hypersensitivity reactions and dermatologic toxicity may occur in patients taking mesna; therefore, if either reaction occurs, mesna should be discontinued and patient should be provided with supportive care.
- Affected organisms
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
References
- General References
- Matz EL, Hsieh MH: Review of Advances in Uroprotective Agents for Cyclophosphamide and Ifosfamide-Induced Hemorrhagic Cystitis. Urology. 2016 Aug 23. pii: S0090-4295(16)30458-7. doi: 10.1016/j.urology.2016.07.030. [PubMed:27566144]
- Cutler MJ, Urquhart BL, Velenosi TJ, Meyer Zu Schwabedissen HE, Dresser GK, Leake BF, Tirona RG, Kim RB, Freeman DJ: In vitro and in vivo assessment of renal drug transporters in the disposition of mesna and dimesna. J Clin Pharmacol. 2012 Apr;52(4):530-42. doi: 10.1177/0091270011400414. Epub 2011 Apr 19. [PubMed:21505084]
- DynaMed [Link]
- External Links
- Human Metabolome Database
- HMDB0003745
- KEGG Compound
- C03576
- PubChem Compound
- 598
- PubChem Substance
- 310265029
- ChemSpider
- 578
- ChEBI
- 17905
- ChEMBL
- CHEMBL1098319
- HET
- COM
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Coenzyme_M
- ATC Codes
- R05CB05 — Mesna
- R05CB — Mucolytics
- R05C — EXPECTORANTS, EXCL. COMBINATIONS WITH COUGH SUPPRESSANTS
- R05 — COUGH AND COLD PREPARATIONS
- R — RESPIRATORY SYSTEM
- AHFS Codes
- 92:56.00 — Protective Agents
- PDB Entries
- 1e6v / 1e6y / 1hbn / 1hbo / 1hbu / 1mro / 2c3c / 2c3d / 3m1v / 3m2r … show 25 more
- FDA label
- Download (3.61 MB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Injection, solution Intravenous 100 mg/mL Solution Intravenous 100 mg/mL Tablet, film coated Oral 400 mg/1 Solution Intravenous 100 mg Solution Intravenous; Oral 100 mg Liquid Intravenous; Oral 100 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 12.7 mg/mL ALOGPS logP -1.5 ALOGPS logP -0.4 ChemAxon logS -1 ALOGPS pKa (Strongest Acidic) -1.2 ChemAxon pKa (Strongest Basic) -9.6 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 54.37 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 29.13 m3·mol-1 ChemAxon Polarizability 12.54 Å3 ChemAxon Number of Rings 0 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key GC-MS Spectrum - GC-MS (2 TMS) GC-MS splash10-00e9-7960000000-d0e9fc5f5629ba893d57 Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available GC-MS Spectrum - GC-MS GC-MS splash10-00e9-7960000000-d0e9fc5f5629ba893d57 GC-MS Spectrum - GC-EI-TOF GC-MS splash10-052u-2900000000-51cd7c5f2497db0c7a15 GC-MS Spectrum - GC-EI-TOF GC-MS splash10-004m-7970000000-a5c3c33a78b251bdd12c 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 LC-MS/MS Spectrum - LC-ESI-QTOF , negative LC-MS/MS splash10-001i-9400000000-f69174f630c88b6e6c0b
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as organosulfonic acids. These are compounds containing the sulfonic acid group, which has the general structure RS(=O)2OH (R is not a hydrogen atom).
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Organic sulfonic acids and derivatives
- Sub Class
- Organosulfonic acids and derivatives
- Direct Parent
- Organosulfonic acids
- Alternative Parents
- Sulfonyls / Alkanesulfonic acids / Alkylthiols / Organic oxides / Hydrocarbon derivatives
- Substituents
- Alkanesulfonic acid / Sulfonyl / Organosulfonic acid / Alkylthiol / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organosulfur compound / Aliphatic acyclic compound
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- thiol, organosulfonic acid (CHEBI:17905)
Enzymes
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Substrate
- General Function
- Nadp binding
- Specific Function
- Maintains high levels of reduced glutathione in the cytosol.
- Gene Name
- GSR
- Uniprot ID
- P00390
- Uniprot Name
- Glutathione reductase, mitochondrial
- Molecular Weight
- 56256.565 Da
References
- Ormstad K, Orrenius S, Lastbom T, Uehara N, Pohl J, Stekar J, Brock N: Pharmacokinetics and metabolism of sodium 2-mercaptoethanesulfonate in the rat. Cancer Res. 1983 Jan;43(1):333-8. [PubMed:6401168]
Drug created on September 17, 2015 15:16 / Updated on July 21, 2018 18:01