brequinar   Click here for help

GtoPdb Ligand ID: 7406

Synonyms: DUP-785 | DUP785 | NSC 368390 | NSC-368390 | NSC368390
PDB Ligand
Compound class: Synthetic organic
Comment: Brequinar inhibits dihydroorotate dehydrogenase (DHODH), the fourth enzyme in the de novo pyrimidine biosynthesis pathway [2], and it depletes cells of the precursors that are critical for RNA and DNA synthesis [3]. It was developed for potential anti-neoplastic activity. The drug exhibits anti-neoplastic activity against refractory solid tumours in preclinical models, with continuous treatment being necessary to effectively deplete pyrimidine pools in the cancer cells and cause tumour inhibition [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

brequinar is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 3
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 50.19
Molecular weight 375.11
XLogP 6.26
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Fc1ccc2c(c1)c(C(=O)O)c(c(n2)c1ccc(cc1)c1ccccc1F)C
Isomeric SMILES Fc1ccc2c(c1)c(C(=O)O)c(c(n2)c1ccc(cc1)c1ccccc1F)C
InChI InChI=1S/C23H15F2NO2/c1-13-21(23(27)28)18-12-16(24)10-11-20(18)26-22(13)15-8-6-14(7-9-15)17-4-2-3-5-19(17)25/h2-12H,1H3,(H,27,28)
InChI Key PHEZJEYUWHETKO-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Brequinar has been advanced to Phase 1/2 clinical evaluation in patiets with acute myeloid leukemia. With the recognition that DHODH inhibitors can have antiviral activity by limiting the supply of host-produced pyrimidines that viruses need to replicate, brequinar is being evaluated in patients with COVID-19 (the clinical manifestation of SARS-CoV-2 infection).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Brequinar inhibits dihydroorotate dehydrogenase (DHODH), the fourth enzyme in the de novo pyrimidine biosynthesis pathway. Pyrimidines are essential for DNA and RNA synthesis and are therefore crucial for cell growth and division.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04425252 Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Patients With COVID-19 Phase 1/Phase 2 Interventional Clear Creek Bio, Inc.
NCT03760666 A Study of Brequinar in Subjects With Relapsed/Refractory Acute Myeloid Leukemia Phase 1/Phase 2 Interventional Clear Creek Bio, Inc.