Gimeracil
Explore a selection of our essential drug information below, or:
Overview
- Description
- A medication given to boost the effectiveness of anticancer drugs.
- Description
- A medication given to boost the effectiveness of anticancer drugs.
- DrugBank ID
- DB09257
- Type
- Small Molecule
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 9
- Phase 2
- 64
- Phase 3
- 31
- Phase 4
- 3
- Mechanism of Action
Identification
- Summary
Gimeracil is a DPD inhibitor used as an adjunct to antineoplastic therapy to increase the systemic concentrations and therapeutic effectiveness of other antineoplastic agents.
- Brand Names
- Teysuno
- Generic Name
- Gimeracil
- DrugBank Accession Number
- DB09257
- Background
Gimeracil is an adjunct to antineoplastic therapy, used to increase the concentration and effect of the main active componets within chemotherapy regimens. Approved by the European Medicines Agency (EMA) in March 2011, Gimeracil is available in combination with Oteracil 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.
Gimeracil's main role within Teysuno is to prevent the breakdown of Fluorouracil (5-FU), which helps to maintin high enough concentrations for sustained effect against cancer cells 2. It functions by reversibly and selectively blocking the enzyme dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU 1. This allows higher concentrations of 5-FU to be achieved with a lower dose of tegafur, thereby also reducing toxic side effects.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 145.54
Monoisotopic: 144.9930561 - Chemical Formula
- C5H4ClNO2
- Synonyms
- 5-Chloro-2,4-dihydroxypyridine
- 5-Chloro-4-hydroxy-2-pyridone
- Gimeracil
- gimestat
- Teysuno
- Ts-1 (TN)
- External IDs
- Ts-1 (TN)
Pharmacology
- Indication
Gimeracil is used as an adjunct to antineoplastic therapy. When used within the product Teysuno, gimeracil is indicated for the treatment of adults with advanced gastric (stomach) cancer when given in combination with cisplatin.
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 Advanced gastric cancer Regimen in combination with: Tegafur (DB09256), Oteracil (DB03209), Cisplatin (DB00515) •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Not Available
- Mechanism of action
Gimeracil's main role within Teysuno is to prevent the breakdown of Fluorouracil (5-FU), which helps to maintin high enough concentrations for sustained effect against cancer cells 2. It functions by reversibly blocking the enzyme dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU 1.
Target Actions Organism ADihydropyrimidine dehydrogenase [NADP(+)] inhibitorHumans - Absorption
Mean 5-FU maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) values were approximately 3-fold higher after Teysuno administration than after administration of tegafur alone, despite a 16-fold lower Teysuno dose (50 mg of tegafur) compared to tegafur alone (800 mg), and are attributed to inhibition of DPD by gimeracil. Maximum plasma uracil concentration was observed at 4 hours, with a return to baseline levels within approximately 48 hours after dosing, indicating the reversibility of the DPD inhibition by gimeracil.
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 2.
- 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 2.
- Protein binding
Oteracil, gimeracil, 5-FU, and tegafur are 8.4%, 32.2%, 18.4%, and 52.3% protein bound, respectively 2.
- Metabolism
- Not Available
- 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 2.
- 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 2.
- 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
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 softwareAbacavir Abacavir may decrease the excretion rate of Gimeracil which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Gimeracil which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Gimeracil which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Gimeracil which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Gimeracil which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- Drink plenty of fluids. Drinking water is important to prevent dehydration when taking Teysuno.
- Take on an empty stomach. Take Teysuno at least 1 hour before or 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.
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image TEYSUNO Gimeracil (4.35 mg) + Oteracil (11.8 mg) + Tegafur (15 mg) Capsule Oral Nordic Group Bv 2014-07-08 Not applicable Italy Teysuno Gimeracil (5.8 mg) + Oteracil (15.8 mg) + Tegafur (20 mg) Capsule Oral Nordic Group Bv 2016-09-08 Not applicable EU TEYSUNO Gimeracil (5.8 mg) + Oteracil (15.8 mg) + Tegafur (20 mg) Capsule Oral Nordic Group Bv 2014-07-08 Not applicable Italy TEYSUNO Gimeracil (4.35 mg) + Oteracil (11.8 mg) + Tegafur (15 mg) Capsule Oral Nordic Group Bv 2014-07-08 Not applicable Italy Teysuno Gimeracil (4.35 mg) + Oteracil (11.8 mg) + Tegafur (15 mg) Capsule Oral Nordic Group Bv 2016-09-08 Not applicable EU
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyridinones. These are compounds containing a pyridine ring, which bears a ketone.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Hydropyridines
- Direct Parent
- Pyridinones
- Alternative Parents
- Hydroxypyridines / Dihydropyridines / Aryl chlorides / Vinylogous acids / Heteroaromatic compounds / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds show 3 more
- Substituents
- Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Dihydropyridine / Heteroaromatic compound / Hydrocarbon derivative / Hydroxypyridine / Lactam / Organic nitrogen compound show 9 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- UA8SE1325T
- CAS number
- 103766-25-2
- InChI Key
- ZPLQIPFOCGIIHV-UHFFFAOYSA-N
- InChI
- InChI=1S/C5H4ClNO2/c6-3-2-7-5(9)1-4(3)8/h1-2H,(H2,7,8,9)
- IUPAC Name
- 5-chloro-4-hydroxy-1,2-dihydropyridin-2-one
- SMILES
- OC1=CC(=O)NC=C1Cl
References
- General References
- Harada K, Ferdous T, Harada T, Takenawa T, Ueyama Y: Gimeracil enhances the antitumor effect of cisplatin in oral squamous cell carcinoma cells in vitro and in vivo. Oncol Lett. 2017 Sep;14(3):3349-3356. doi: 10.3892/ol.2017.6602. Epub 2017 Jul 18. [Article]
- European Medicines Agency (EMA): TEYSUNO (tegafur/gimeracil/oteracil) Summary of Product Characteristics [Link]
- External Links
- Human Metabolome Database
- HMDB0252719
- KEGG Drug
- D01846
- PubChem Compound
- 54679224
- PubChem Substance
- 310265159
- ChemSpider
- 3353
- ChEBI
- 31652
- ChEMBL
- CHEMBL1730601
- ZINC
- ZINC000013831809
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 Enrolling by Invitation Not Available Solid Tumors 1 somestatus stop reason just information to hide Not Available Recruiting Treatment Gastric Cancer/Adenocarcinoma of Esophagogastric Junction 1 somestatus stop reason just information to hide 4 Not Yet Recruiting Treatment Gastric Cancer 1 somestatus stop reason just information to hide 4 Unknown Status Treatment Unresectable Pancreatic Cancer 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Gastric Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, orally disintegrating; tablet, soluble Oral Capsule Oral Tablet Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 14.2 mg/mL ALOGPS logP -0.08 ALOGPS logP 0.13 Chemaxon logS -1 ALOGPS pKa (Strongest Acidic) 8.66 Chemaxon pKa (Strongest Basic) -4.5 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 49.33 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 34.65 m3·mol-1 Chemaxon Polarizability 12.19 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0900000000-33d1264769de491005ca Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-2900000000-f470cbbd11a33eda7687 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-3900000000-3f85c2d9cc6aa5328619 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9400000000-875d40e8b0318330bc9d Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03dl-9000000000-e2ae28c12f5e9814f240 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9000000000-cd5d396f1538a7e5ba1b 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]- 122.83591 predictedDeepCCS 1.0 (2019) [M+H]+ 125.105896 predictedDeepCCS 1.0 (2019) [M+Na]+ 133.65666 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Involved in pyrimidine base degradation (PubMed:1512248). Catalyzes the reduction of uracil and thymine (PubMed:1512248). Also involved the degradation of the chemotherapeutic drug 5-fluorouracil (PubMed:1512248)
- Specific Function
- 4 iron, 4 sulfur cluster binding
- Gene Name
- DPYD
- Uniprot ID
- Q12882
- Uniprot Name
- Dihydropyrimidine dehydrogenase [NADP(+)]
- Molecular Weight
- 111400.32 Da
References
- European Medicines Agency (EMA): TEYSUNO (tegafur/gimeracil/oteracil) Summary of Product Characteristics [Link]
Drug created at October 26, 2015 16:31 / Updated at November 05, 2024 05:14