Oteracil
Identification
- Summary
Oteracil is a chemotherapy agent used in combination with tegafur, cisplatin and gimeracil to treat advanced gastric cancer.
- Brand Names
- Teysuno
- Generic Name
- Oteracil
- DrugBank Accession Number
- DB03209
- Background
Oteracil is an adjunct to antineoplastic therapy, used to reduce the toxic side effects associated with chemotherapy. Approved by the European Medicines Agency (EMA) in March 2011, Oteracil is available in combination with Gimeracil and Tegafur within the commercially available product "Teysuno". The main active ingredient in Teysuno is Tegafur, a pro-drug of Fluorouracil (5-FU), which is a cytotoxic anti-metabolite drug that acts on rapidly dividing cancer cells. By mimicking a class of compounds called "pyrimidines" that are essential components of RNA and DNA, 5-FU is able to insert itself into strands of DNA and RNA, thereby halting the replication process necessary for continued cancer growth.
Oteracil's main role within Teysuno is to reduce the activity of 5-FU within normal gastrointestinal mucosa, and therefore reduce's gastrointestinal toxicity 1. It functions by blocking the enzyme orotate phosphoribosyltransferase (OPRT), which is involved in the production of 5-FU.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 157.0843
Monoisotopic: 157.012355599 - Chemical Formula
- C4H3N3O4
- Synonyms
- 5-azaorotic acid
- Allantoxanic acid
- Oteracil
- Oxonate
- Oxonic Acid
Pharmacology
- Indication
Oteracil is used as an adjunct to antineoplastic therapy. When used within the product Teysuno, oteracil is indicated for the treatment of adults with advanced gastric (stomach) cancer when given in combination with cisplatin.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Advanced gastric cancer Regimen in combination with: Cisplatin (DB00515), Tegafur (DB09256), Gimeracil (DB09257) •••••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Not Available
- Mechanism of action
Oteracil's main role within Teysuno is to reduce the activity of 5-FU within normal gastrointestinal mucosa, and therefore reduce's gastrointestinal toxicity 1. It functions by blocking the enzyme orotate phosphoribosyltransferase (OPRT), which is involved in the production of 5-FU.
- Absorption
After administration of a single dose of 50 mg Teysuno (expressed as tegafur content), median Tmax for Teysuno components tegafur, gimeracil, and oteracil was 0.5, 1.0, and 2.0 hours, respectively 1.
- Volume of distribution
Although no intravenous data are available for Teysuno in humans, the volume of distribution could be roughly estimated from the apparent volume of distribution and urinary excretion data as 16 l/m2, 17 l/m2, and 23 l/m2 for tegafur, gimeracil and oteracil, respectively 1.
- Protein binding
Oteracil, gimeracil, 5-FU, and tegafur are 8.4%, 32.2%, 18.4%, and 52.3% protein bound, respectively 1.
- Metabolism
Based on the results of in vitro studies, a part of oteracil is non-enzymatically degraded to 5-azauracil (5-AZU) by gastric fluid, and is then converted to cyanuric acid (CA) in the digestive tract. Only a small amount of oteracil is metabolised in the liver because of its low permeability 1.
- Route of elimination
Following a single dose of Teysuno, approximately 3.8% to 4.2% of administered tegafur, 65% to 72% of administered gimeracil, and 3.5% to 3.9% of administered oteracil were excreted unchanged in the urine 1.
- Half-life
Following a single dose of Teysuno, T1/2 values ranged from 6.7 to 11.3 hours for tegafur, from 3.1 to 4.1 hours for gimeracil, and from 1.8 to 9.5 hours for oteracil 1.
- Clearance
Not Available
- Adverse Effects
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- Toxicity
Not Available
- 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 softwareAllopurinol The therapeutic efficacy of Oteracil can be decreased when used in combination with Allopurinol. - Food Interactions
- Take separate from meals. Oteracil should be separated from meals by at least one hour before and after eating.
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.
- Product Ingredients
Ingredient UNII CAS InChI Key Oteracil potassium 4R7FFA00RX 2207-75-2 IAPCTXZQXAVYNG-UHFFFAOYSA-M - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image TEYSUNO Oteracil (15.8 mg) + Gimeracil (5.8 mg) + Tegafur (20 mg) Capsule Oral Nordic Group Bv 2014-07-08 Not applicable Italy TEYSUNO Oteracil (11.8 mg) + Gimeracil (4.35 mg) + Tegafur (15 mg) Capsule Oral Nordic Group Bv 2014-07-08 Not applicable Italy Teysuno Oteracil (15.8 mg) + Gimeracil (5.8 mg) + Tegafur (20 mg) Capsule Oral Nordic Group Bv 2016-09-08 Not applicable EU Teysuno Oteracil (11.8 mg) + Gimeracil (4.35 mg) + Tegafur (15 mg) Capsule Oral Nordic Group Bv 2016-09-08 Not applicable EU TEYSUNO Oteracil (11.8 mg) + Gimeracil (4.35 mg) + Tegafur (15 mg) Capsule Oral Nordic Group Bv 2014-07-08 Not applicable Italy
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as triazinones. These are compounds containing a triazine ring which bears a ketone group a carbon atom.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Triazines
- Sub Class
- Triazinones
- Direct Parent
- Triazinones
- Alternative Parents
- 1,3,5-triazines / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- 1,3,5-triazine / Aromatic heteromonocyclic compound / Azacycle / Carboxylic acid / Carboxylic acid derivative / Heteroaromatic compound / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Organic nitrogen compound / Organic oxide
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- monocarboxylic acid, 1,3,5-triazines (CHEBI:30863)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 5VT6420TIG
- CAS number
- 937-13-3
- InChI Key
- RYYCJUAHISIHTL-UHFFFAOYSA-N
- InChI
- InChI=1S/C4H3N3O4/c8-2(9)1-5-3(10)7-4(11)6-1/h(H,8,9)(H2,5,6,7,10,11)
- IUPAC Name
- 4,6-dioxo-1,4,5,6-tetrahydro-1,3,5-triazine-2-carboxylic acid
- SMILES
- OC(=O)C1=NC(=O)NC(=O)N1
References
- Synthesis Reference
- US6090940
- General References
- European Medicines Agency (EMA): TEYSUNO (tegafur/gimeracil/oteracil) Summary of Product Characteristics [Link]
- External Links
- KEGG Drug
- D06399
- PubChem Compound
- 4604
- PubChem Substance
- 46508346
- ChemSpider
- 4443
- ChEBI
- 30863
- ChEMBL
- CHEMBL181932
- ZINC
- ZINC000013514753
- PDBe Ligand
- OXC
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Unknown Status Treatment Unresectable Pancreatic Cancer 1 3 Completed Treatment Cervical Cancer 1 3 Completed Treatment Gastric Cancer 2 3 Recruiting Treatment Adjuvant Chemotherapy / Stage III Colorectal Cancer 1 3 Recruiting Treatment Bile Duct Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, soluble Capsule Oral Tablet Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 7.15 mg/mL ALOGPS logP -1.1 ALOGPS logP -1.2 Chemaxon logS -1.3 ALOGPS pKa (Strongest Acidic) 2.14 Chemaxon pKa (Strongest Basic) -2.9 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 107.86 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 29.7 m3·mol-1 Chemaxon Polarizability 11.88 Å3 Chemaxon Number of Rings 1 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 + 0.6506 Blood Brain Barrier + 0.817 Caco-2 permeable - 0.8077 P-glycoprotein substrate Non-substrate 0.703 P-glycoprotein inhibitor I Non-inhibitor 0.9932 P-glycoprotein inhibitor II Non-inhibitor 1.0 Renal organic cation transporter Non-inhibitor 0.9684 CYP450 2C9 substrate Non-substrate 0.705 CYP450 2D6 substrate Non-substrate 0.8199 CYP450 3A4 substrate Non-substrate 0.8073 CYP450 1A2 substrate Non-inhibitor 0.6205 CYP450 2C9 inhibitor Non-inhibitor 0.959 CYP450 2D6 inhibitor Non-inhibitor 0.9326 CYP450 2C19 inhibitor Non-inhibitor 0.9364 CYP450 3A4 inhibitor Non-inhibitor 0.935 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 1.0 Ames test Non AMES toxic 0.9277 Carcinogenicity Non-carcinogens 0.9449 Biodegradation Ready biodegradable 0.5369 Rat acute toxicity 1.6818 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9804 hERG inhibition (predictor II) Non-inhibitor 0.9803
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 126.43561 predictedDeepCCS 1.0 (2019) [M+H]+ 129.59004 predictedDeepCCS 1.0 (2019) [M+Na]+ 138.5015 predictedDeepCCS 1.0 (2019)
Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:52