EPZ015666   Click here for help

GtoPdb Ligand ID: 8287

Synonyms: EPZ 015666 | EPZ-015666
PDB Ligand
Compound class: Synthetic organic
Comment: EPZ015666 is a first-in-class, potent, selective and orally bioavailable PRMT5 inhibitor. The pharmaceutical composition may comprise the hydrochloride salt. EPZ015666 is compound 166 in patent WO2014100719 [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

EPZ015666 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 3
Rotatable bonds 8
Topological polar surface area 99.61
Molecular weight 383.2
XLogP -0.03
No. Lipinski's rules broken 0

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 OC(CN1CCc2c(C1)cccc2)CNC(=O)c1ncnc(c1)NC1COC1
Isomeric SMILES O[C@H](CN1CCc2c(C1)cccc2)CNC(=O)c1ncnc(c1)NC1COC1
InChI InChI=1S/C20H25N5O3/c26-17(10-25-6-5-14-3-1-2-4-15(14)9-25)8-21-20(27)18-7-19(23-13-22-18)24-16-11-28-12-16/h1-4,7,13,16-17,26H,5-6,8-12H2,(H,21,27)(H,22,23,24)/t17-/m0/s1
InChI Key ZKXZLIFRWWKZRY-KRWDZBQOSA-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
EPZ015666 shows anti-tumour effects in preclinical in vitro and in vivo studies. EPZ015666 demonstrates dose-dependent inhibition of intracellular symmetric arginine di-methylation of SmD3, a PRMT5 substrate involved in RNA processing.
Pending publication of a peer reviewed article, data presented here was taken from Epizyme's poster 'Identification of a First-In-Class PRMT5 Inhibitor with Potent in Vitro and In Vivo Activity in Preclinical Models of Mantle Cell Lymphoma' presented at the 56th annual meeting of the American Society of Hematology (ASH) in San Francisco (2014). This poster reports that EPZ015666 is >20,000-fold selective for PRMT5 compared to other protein methyltransferases (PMTs) tested. Patent WO2014100719 [5] provides a binned biochemical IC50 of < 100nM for this compound (compound 166 in the patent document).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
protein arginine methyltransferase 5 Primary target of this compound Hs Inhibitor Inhibition 8.3 pKi -
⤷ pKi 8.3 (Ki 5x10-9 M)