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zapnometinib   Click here for help

GtoPdb Ligand ID: 11679

Synonyms: ATR-002 | ATR002 | PD-0184264 | PD0184264
Compound class: Synthetic organic
Comment: We obtained the chemical structure for zapnometinib from WHO Proposed list 125 of July 2021. This mapped to PubChem CID 10112191, and via ChEMBL to the MEK serine/threonine protein kinases inhibitor PD-0184264 [1]. PD-0184264 is an oral MEK inhibitor that targets the Raf/MEK/ERK signalling pathway. This pathway is exploited (activated) by several species of RNA viruses (e.g. influenza viruses, hantaviruses, respiratory syncytial viruses and coronaviruses) for their successful replication. Blocking the host Raf/MEK/ERK signalling pathway inhibits formation of fully-formed virus particles in infected cells, and reduces viral load. At the same time, inhibiting MEK provides potential to modulate the immune response induced during infection. In COVID-19 zapnometinib is predicted to reduce expression of pro-inflammatory cytokines and/or chemokines (e.g. TNF-α, IL-1β, CXCL10/IP-10, CXCL8/IL-8, CCL2/MCP-1 and CCL3/MIP-1α) that drive the destructive hyperinflammation in patients with severe disease.
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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

zapnometinib 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 2
Rotatable bonds 3
Topological polar surface area 49.33
Molecular weight 408.92
XLogP 5.29
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 Ic1ccc(c(c1)Cl)Nc1c(ccc(c1F)F)C(=O)O
Isomeric SMILES Clc1c(Nc2c(C(=O)O)ccc(c2F)F)ccc(c1)I
InChI InChI=1S/C13H7ClF2INO2/c14-8-5-6(17)1-4-10(8)18-12-7(13(19)20)2-3-9(15)11(12)16/h1-5,18H,(H,19,20)
InChI Key XCNBGWKQXRQKSA-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/)
References
1. Tecle H, Shao J, Li Y, Kothe M, Kazmirski S, Penzotti J, Ding YH, Ohren J, Moshinsky D, Coli R et al.. (2009)
Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?.
Bioorg Med Chem Lett, 19 (1): 226-9. [PMID:19019675]