S312   Click here for help

GtoPdb Ligand ID: 11163

Synonyms: compound 19 [PMID: 26443076]
PDB Ligand
Compound class: Synthetic organic
Comment: S312 is an inhibitor of dihydroorotate dehydrogenase (DHODH) [2]. It was initially designed and reported for application as an anti-inflammatory agent [1] and was effective in a mouse rheumatoid arthritis model. S312 has most recently been explored for antiviral activity against RNA viruses, including influenza virus strains, Zika and Ebola viruses and SARS-CoV-2, based on the rationale that viruses depend on host pyrimidine synthesis to maintain their replication rate, and that therefore inhibiting a crucial step in this synthetic pathway has potential to limit viral replication. Mechanistically, S312 binds at the putative ubiquinone binding tunnel within the DHODH active site.
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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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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 5
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 102.82
Molecular weight 357.03
XLogP 5.41
No. Lipinski's rules broken 1
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 Clc1ccccc1c1csc(n1)N/N=C/c1ccccc1C(=O)O
Isomeric SMILES Clc1ccccc1c1csc(n1)N/N=C/c1ccccc1C(=O)O
InChI InChI=1S/C17H12ClN3O2S/c18-14-8-4-3-7-13(14)15-10-24-17(20-15)21-19-9-11-5-1-2-6-12(11)16(22)23/h1-10H,(H,20,21)(H,22,23)/b19-9+
InChI Key DDEIFUOYHWEWSS-DJKKODMXSA-N
Bioactivity Comments
S312 is a more potent inhibitor of DHODH than teriflunomide in vitro [2]. Antiviral potency (EC50) for S312 vs. SARS-CoV-2 is 1.56 μM at MOI = 0.05. In comparison teriflunomide had an anti-SARS-CoV-2 EC50 of 26.06 μM, the EC50 for favipiravir was 66.85 μM and for brequinar it was 0.123 μM.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
dihydroorotate dehydrogenase (quinone) Hs Inhibitor Binding 7.7 pKd - 2
⤷ pKd 7.7 (Kd 2.03x10-8 M) [2]
dihydroorotate dehydrogenase (quinone) Hs Inhibitor Inhibition 7.5 pIC50 - 2
⤷ pIC50 7.5 (IC50 2.92x10-8 M) [2]