ensitrelvir   Click here for help

GtoPdb Ligand ID: 11871

Synonyms: compound 3 [PMID: 35352927] | compound I-0006 [WO2022138987] [3] | S-217622 | S217622 | Xocova®
Approved drug PDB Ligand
ensitrelvir is an approved drug (Japan (2024))
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 [4]. 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) [5].
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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 1
Rotatable bonds 5
Topological polar surface area 99.96
Molecular weight 531.11
XLogP 4.25
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 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)
InChI Key QMPBBNUOBOFBFS-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
SARS-CoV-2 Infection: Ensitrelvir (S-217622) was advanced to Phase 2/3 clinical evaluation in Japan (JRCT ID: jRCT2031210350) [1]. Volunteers were recruited to Phase 3 study NCT05305547,a collaboration between Shiongi and the US National Institute of Allergy and Infectious Diseases (NIAID), which enrolled >2000 individuals. In November 2022, ensitrelvir (Xocova®) was authorised by the Japanese regulator, under their emergency approval scheme. Regular approval was granted in Japan in March 2024, for Xocova® (ensitrelvir fumaric acid formulation), as the first single-entity, nonpeptidic, noncovalent, small molecule SARS-CoV-2 main protease inhibitor drug to treat COVID-19 [2].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT05409911 A Study to Assess S-217622 in Participants With Mild and Moderate Hepatic Impairment and Healthy Control Participants Phase 1 Interventional Shionogi Inc.
NCT05363215 A Study to Assess S-217622 in Participants With Renal Impairment and Healthy Participants Phase 1 Interventional Shionogi Inc.
NCT05305547 A Study to Compare S-217622 With Placebo in Non-Hospitalized High-Risk Participants With COVID-19 Phase 3 Interventional Shionogi Inc.