ensitrelvir   Click here for help

GtoPdb Ligand ID: 11871

Synonyms: compound 3 [PMID: 35352927] | compound I-0006 [WO2022138987] [2] | S-217622 | S217622 | Xocova®
Approved drug PDB Ligand
ensitrelvir is an approved drug (Japan 2022)
Compound class: Synthetic organic
Comment: Ensitrelvir is a newly proposed INN for an antiviral that was revealed in January 2022, in the COVID special section of Proposed List 126. It was therefore assumed to target SARS-CoV-2, and to be a potential drug for the treatment of patients with SARS-CoV-2 infection (COVID-19). We were able to match this chemical structure to the Shiongi lead compound S-217622, following their preprint disclosure. The Shiongi article was subsequently published in J Med Chem in March 2022 [3]. S-217622 is described as a non-covalent oral Mpro inhibitor, with pharmacokinetics that support once-daily dosing. It was formulated as a 1:1 fumaric acid complex. Molecular dynamics simulation has been used to estimate ensitrelvir's effectiveness against 6 common SARS-CoV-2 variants (Alpha AP.1, Beta B.1.351, Gamma P.1.13, Delta AY.116, Omicron BA.1/2/3/4/5 and Lambda C.37) [4].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 99.96
Molecular weight 531.11
XLogP 4.25
No. Lipinski's rules broken 0
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Canonical SMILES Cn1cnc(n1)Cn1c(=O)[nH]/c(=N\c2cc3cn(nc3cc2Cl)C)/n(c1=O)Cc1cc(F)c(cc1F)F
Isomeric SMILES Clc1c(cc2cn(nc2c1)C)/N=c/1\[nH]c(=O)n(c(=O)n1Cc1c(cc(c(c1)F)F)F)Cc1nn(cn1)C
InChI InChI=1S/C22H17ClF3N9O2/c1-32-7-12-4-18(13(23)5-17(12)30-32)28-20-29-21(36)35(9-19-27-10-33(2)31-19)22(37)34(20)8-11-3-15(25)16(26)6-14(11)24/h3-7,10H,8-9H2,1-2H3,(H,28,29,36)
Bioactivity Comments
S-217622 is active (in vitro) against SARS-CoV-2 variants that were in circulation during the period of its development, and it has antiviral activity against other coronavirus strains (MERS-CoV, SARS-CoV, HCoV-229E and HCoV-OC43).
Selectivity at other protein targets
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
CoV 3C-like (main) protease SARS-CoV-2 Inhibitor Inhibition 7.9 pIC50 - 3
pIC50 7.9 (IC50 1.3x10-8 M) [3]