In vitro activity: EBI-2511 is a novel and orally available benzofuran derived EZH2 inhibitors that was discovered through a scaffold hopping approach based on the clinical compound of EPZ-6438. It has the potential for treatment of Non-Hodgkin’s Lymphoma. Further rational structure-activity relationship exploration and optimization led to the discovery of more potent EZH2 inhibitors with oral bioavailability in mice and rats. EBI-2511 demonstrated excellent in vivo efficacy in Pfeiffer tumor Xenograft models in mouse and is under preclinical development for the treatment of cancers associated with EZH2 mutations.

Kinase Assay: EBI-2511 is a highly potent and orally active EZH2 inhibitor, with an IC50 of 6 nM in Pfeffiera cell lines, respectively.

Cell Assay: EBI-2511 (Compound 34) significantly reduces cellular H3K27me3 levels in a dose-dependent manner with an approximate IC50 of 8 nM, which is 3-fold more potent than EPZ-6438. In addition to Pfeffier cell line, EBI-2511 was shown active with IC50 value of 55 nM against WSU-DLCL2.