S416   Click here for help

GtoPdb Ligand ID: 11164

Compound class: Synthetic organic
Comment: S416 is an inhibitor of dihydroorotate dehydrogenase (DHODH) [1]. It has been explored for antiviral activity against RNA viruses, including SARS-CoV-2, based on the rationale that viruses depend on host pyrimidine synthesis to maintain their replication, and that therefore inhibiting a crucial step in this synthetic pathway should limit viral replication. Mechanistically, S416 binds at the putative ubiquinone binding tunnel within the DHODH active site.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 94.03
Molecular weight 371.05
XLogP 4.82
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES CN(c1scc(n1)c1ccccc1Cl)/N=C/c1ccccc1C(=O)O
Isomeric SMILES CN(c1scc(n1)c1ccccc1Cl)/N=C/c1ccccc1C(=O)O
InChI InChI=1S/C18H14ClN3O2S/c1-22(20-10-12-6-2-3-7-13(12)17(23)24)18-21-16(11-25-18)14-8-4-5-9-15(14)19/h2-11H,1H3,(H,23,24)/b20-10+
InChI Key MWIQPUXVXAVFRM-KEBDBYFISA-N
Bioactivity Comments
S416 is a more potent inhibitor of DHODH than teriflunomide in vitro [1]. Antiviral potency (EC50) for S416 vs. SARS-CoV-2 is 17 nM 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
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
dihydroorotate dehydrogenase (quinone) Hs Inhibitor Binding 8.8 pKd - 1
pKd 8.8 (Kd 1.69x10-9 M) [1]
dihydroorotate dehydrogenase (quinone) Hs Inhibitor Inhibition 8.1 pIC50 - 1
pIC50 8.1 (IC50 7.5x10-9 M) [1]