Ligand id: 8287

Name: EPZ015666

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 99.61
Molecular weight 383.2
XLogP 1.31
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

View interactive charts of activity data from GtoPdb and ChEMBL (where available) across species

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 Affinity Units Concentration range (M) Reference
protein arginine methyltransferase 5 Hs Inhibitor Inhibition 8.3 pKi -
pKi 8.3 (Ki 5x10-9 M)