zeprumetostat   Click here for help

GtoPdb Ligand ID: 13512

Synonyms: compound 2 [WO2017084494] | compound Ia [WO2019091450]
Compound class: Synthetic organic
Comment: The chemical structure for zeprumetostat was obtained from WHO proposed INN list 131 (August 2024). The INN record describes the compound as an enhancer of zeste homolog 2 (EZH2) inhibitor and antineoplastic. The chemical structure is claimed in patent WO2017084494A1 [1]. Based on Hengrui's declared development pipeline, we predict that zeprumetostat is the INN for their EZH2 inhibitor clinical lead SHR2554.
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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

zeprumetostat 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 8
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 83.14
Molecular weight 548.72
XLogP 3.59
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 CCC1=C(C=C2C(=C1C(=O)NCC3=C(C)C=C(C)NC3=O)C=C(CN4CCCCC4)O2)N(CC)C5CCOCC5
Isomeric SMILES CCC1=C(C2=C(C=C1N(CC)C3CCOCC3)OC(=C2)CN4CCCCC4)C(=O)NCC5=C(C=C(NC5=O)C)C
InChI InChI=1S/C32H44N4O4/c1-5-25-28(36(6-2)23-10-14-39-15-11-23)18-29-26(17-24(40-29)20-35-12-8-7-9-13-35)30(25)32(38)33-19-27-21(3)16-22(4)34-31(27)37/h16-18,23H,5-15,19-20H2,1-4H3,(H,33,38)(H,34,37)
InChI Key YLZVNQZYAYVUCW-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/)
Bioactivity Comments
Against a panel of histone and DNA methyltransferases SHR2554 inhibits only EZH2 and EZH1 [4].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
enhancer of zeste 2 polycomb repressive complex 2 subunit Hs Inhibitor Inhibition 8.2 – 9.1 pIC50 - 1,4
⤷ pIC50 9.1 (IC50 8.7x10-10 M) [4]
Description: Inhibition of WT EZH2 methyltransferase activity
pIC50 8.4 (IC50 4x10-9 M) [1]
Description: Inhibition of EZH2Y641F-catalysed H3K27Me3 methylation
pIC50 8.2 (IC50 5.7x10-9 M) [1]
Description: Inhibition of EZH2A677G-catalysed H3K27Me3 methylation
enhancer of zeste 1 polycomb repressive complex 2 subunit Hs Inhibitor Inhibition 7.7 pIC50 - 4
⤷ pIC50 7.7 (IC50 1.91x10-8 M) [4]
Description: Inhibition of WT EZH1 methyltransferase activity