Eniluracil
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Eniluracil
- DrugBank Accession Number
- DB03516
- Background
Eniluracil, which was previously under development by GlaxoSmithKline (GSK), is being developed by Adherex to enhance the therapeutic value and effectiveness of 5-fluorouracil (5-FU), one of the world’s most widely-used oncology agents. 5-FU is widely used in the U.S. and is often first or second line therapy for a variety of cancers including colorectal, breast, gastric, head and neck, ovarian and basal cell cancer of the skin. Eniluracil could improve 5-FU by increasing its effectiveness, reducing its side effects and/or making it orally available. Eniluracil has received Orphan Drug status from the FDA for the treatment of hepatocellular cancer in combination with fluoropyrimidines (including 5-FU).
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 136.1082
Monoisotopic: 136.027277382 - Chemical Formula
- C6H4N2O2
- Synonyms
- 5-Ethynyluracil
- Eniluracil
- External IDs
- 776C85
- Compound 776C
- GW776C85
Pharmacology
- Indication
For the treatment of cancer in combination with 5-fluorouracil.
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- Pharmacodynamics
Eniluracil is an orally active dihydropyrimidine dehydrogenase (DPD) inhibitor, designed to enhance activity of chemotaxic agents. It is under investigation by Adherex, under license from GlaxoSmithKline, for the treatment of cancer in combination with 5-fluorouracil (5-FU).
- Mechanism of action
Normally, 5-FU is rapidly broken down in the body by an enzyme known as dihydropyrimidine dehydrogenase (DPD). Eniluracil irreversibly inhibits DPD, thereby substantially slowing the breakdown of 5-FU and prolonging exposure of the tumor cells to the drug.
Target Actions Organism ADihydropyrimidine dehydrogenase [NADP(+)] modulatorHumans UAldehyde oxidase Not Available Humans UXanthine dehydrogenase/oxidase inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- 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.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrimidones. These are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazines
- Sub Class
- Pyrimidines and pyrimidine derivatives
- Direct Parent
- Pyrimidones
- Alternative Parents
- Hydropyrimidines / Vinylogous amides / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds / Acetylides / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds show 2 more
- Substituents
- Acetylide / Aromatic heteromonocyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine / Lactam / Organic nitrogen compound / Organic oxide / Organic oxygen compound show 6 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 2E2W0W5XIU
- CAS number
- 59989-18-3
- InChI Key
- JOZGNYDSEBIJDH-UHFFFAOYSA-N
- InChI
- InChI=1S/C6H4N2O2/c1-2-4-3-7-6(10)8-5(4)9/h1,3H,(H2,7,8,9,10)
- IUPAC Name
- 5-ethynyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
- SMILES
- O=C1NC=C(C#C)C(=O)N1
References
- General References
- Czito BG, Hong TJ, Cohen DP, Petros WP, Tyler DS, Pappas TN, Yu D, Lee CG, Lockhart AC, Morse MA, Fernando N, Hurwitz HI: A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract. Cancer Invest. 2006 Feb;24(1):9-17. [Article]
- Czito BG, Hong TJ, Cohen DP, Tyler DS, Lee CG, Anscher MS, Ludwig KA, Seigler HF, Mantyh C, Morse MA, Lockhart AC, Petros WP, Honeycutt W, Spector NL, Ertel PJ, Mangum SG, Hurwitz HI: A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):779-85. [Article]
- Yip D, Karapetis C, Strickland AH, Steer C, Holford C, Knight S, Harper P: A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in patients with advanced gastrointestinal malignancies. Ann Oncol. 2003 Jun;14(6):864-6. [Article]
- External Links
- KEGG Drug
- D03998
- PubChem Compound
- 43157
- PubChem Substance
- 175426856
- ChemSpider
- 39327
- BindingDB
- 50124202
- ChEMBL
- CHEMBL355200
- ZINC
- ZINC000000005467
- PDBe Ligand
- Y3G
- PDB Entries
- 7ljs / 7ljt / 7lju
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 data3 Completed Treatment Adenocarcinoma of Colon / Rectal Adenocarcinoma / Recurrent Colon Cancer / Recurrent Rectal Cancer / Stage IV Colon Cancer / Stage IV Rectal Cancer 1 somestatus stop reason just information to hide 2 Completed Treatment Colorectal Cancer 2 somestatus stop reason just information to hide 2 Unknown Status Treatment Metastatic Breast Cancer 1 somestatus stop reason just information to hide 1 Terminated Treatment Breast Cancer / Colon Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.254 mg/mL ALOGPS logP -0.91 ALOGPS logP -0.82 Chemaxon logS -2.7 ALOGPS pKa (Strongest Acidic) 8.54 Chemaxon pKa (Strongest Basic) -6.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 58.2 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 33.39 m3·mol-1 Chemaxon Polarizability 12.05 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 + 0.888 Blood Brain Barrier + 0.9797 Caco-2 permeable - 0.8105 P-glycoprotein substrate Non-substrate 0.7936 P-glycoprotein inhibitor I Non-inhibitor 0.9305 P-glycoprotein inhibitor II Non-inhibitor 1.0 Renal organic cation transporter Non-inhibitor 0.9228 CYP450 2C9 substrate Non-substrate 0.7322 CYP450 2D6 substrate Non-substrate 0.8668 CYP450 3A4 substrate Non-substrate 0.779 CYP450 1A2 substrate Non-inhibitor 0.6875 CYP450 2C9 inhibitor Non-inhibitor 0.9586 CYP450 2D6 inhibitor Non-inhibitor 0.9655 CYP450 2C19 inhibitor Non-inhibitor 0.9685 CYP450 3A4 inhibitor Non-inhibitor 0.9468 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9883 Ames test Non AMES toxic 0.9024 Carcinogenicity Non-carcinogens 0.9454 Biodegradation Ready biodegradable 0.5346 Rat acute toxicity 1.6987 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9667 hERG inhibition (predictor II) Non-inhibitor 0.9515
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-000i-8900000000-dd78f7511ef0363019ea Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-1900000000-8ccff8ca76cd5473fe45 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-3900000000-d15a33add30422c4a7af Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0ftu-9300000000-9cc4449a208346aaf6ac Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9000000000-6b2f88776be86ced1c11 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0gvt-9000000000-e264ecd46a8e729a7bc2 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01ox-9000000000-0298a69bf5d1bb0e0be0 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]- 128.1131104 predictedDarkChem Lite v0.1.0 [M-H]- 124.170044 predictedDeepCCS 1.0 (2019) [M+H]+ 129.0766104 predictedDarkChem Lite v0.1.0 [M+H]+ 127.05307 predictedDeepCCS 1.0 (2019) [M+Na]+ 128.6056104 predictedDarkChem Lite v0.1.0 [M+Na]+ 135.90393 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- 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
- Czito BG, Hong TJ, Cohen DP, Petros WP, Tyler DS, Pappas TN, Yu D, Lee CG, Lockhart AC, Morse MA, Fernando N, Hurwitz HI: A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract. Cancer Invest. 2006 Feb;24(1):9-17. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium and phthalazine, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. May also catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis
- Specific Function
- 2 iron, 2 sulfur cluster binding
- Gene Name
- AOX1
- Uniprot ID
- Q06278
- Uniprot Name
- Aldehyde oxidase
- Molecular Weight
- 147916.735 Da
References
- Porter DJ, Harrington JA, Almond MR, Lowen GT, Zimmerman TP, Spector T: 5-ethynyl-2(1H)-pyrimidinone: aldehyde oxidase-activation to 5-ethynyluracil, a mechanism-based inactivator of dihydropyrimidine dehydrogenase. Biochem Pharmacol. 1994 Mar 29;47(7):1165-71. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro)
- Specific Function
- 2 iron, 2 sulfur cluster binding
- Gene Name
- XDH
- Uniprot ID
- P47989
- Uniprot Name
- Xanthine dehydrogenase/oxidase
- Molecular Weight
- 146422.99 Da
References
- Porter DJ: Reaction of 5-ethynyluracil with rat liver xanthine oxidase. J Biol Chem. 1994 Nov 11;269(45):27932-40. [Article]
Drug created at June 13, 2005 13:24 / Updated at August 26, 2024 19:23