tipiracil   Click here for help

GtoPdb Ligand ID: 8696

Synonyms: MA-1 | TAS-1-462
Approved drug
tipiracil is an approved drug (Japan only)
Compound class: Synthetic organic
Comment: Tipracil is a a uracil derivative that inhibits thymidine phosphorylase (TYMP, P19971; a.k.a. platelet-derived endothelial cell growth factor), an enzyme which metabolises trifluridine.
TAS-102 contains tipracil as the hydrochloride salt (PubChem CID 9903778).

SARS-CoV-2: Tipracil has been shown to bind to the uridine-specific endoribonuclease Nsp15 of SARS-CoV-2, and this interaction inhibits the enzyme's uridine-degrading catalytic activity [1].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 3
Rotatable bonds 2
Topological polar surface area 92.81
Molecular weight 242.06
XLogP 1.26
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES O=c1[nH]c(CN2CCCC2=N)c(c(=O)[nH]1)Cl
Isomeric SMILES O=c1[nH]c(CN2CCCC2=N)c(c(=O)[nH]1)Cl
InChI InChI=1S/C9H11ClN4O2/c10-7-5(12-9(16)13-8(7)15)4-14-3-1-2-6(14)11/h11H,1-4H2,(H2,12,13,15,16)
InChI Key QQHMKNYGKVVGCZ-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Tipracil is a component of the anticancer therapeutic Lonsurf® (code-named TAS-102) [4], which is approved in Japan for the treatment of metastatic/unresectable colorectal cancer. The other component of TAS-102 is trifluridine [3]. In addition, TAS-102 is being assessed in Phase 3 clinical trial for metastatic gastric cancer (NCT02500043).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
By reducing the breakdown of trifluridine, tipiracil improves its antineoplastic activity by increasing its bioavailability.
Thymidine phosphorylase is also reported to be involved in angiogenesis in human gastric cancer [2], suggesting that tipracil may have dual effects when used in combination antineoplastic therapies such as TAS-102.