1. Small-molecule EZH2 inhibitor development.
Small-molecule EZH2 inhibitor development. A, chemical structures of the small-molecule EZH2 inhibitor JQEZ5 and the negative control compound JQEZ23. B, small-molecule inhibitory activity of JQEZ5, JQEZ23, GSK126, and UNC1999 was measured in a five-component PRC2 complex radiometric Scintillation Proximity Assay (SPA) using radiolabeled SAM. C, the IC50 of JQEZ5 as measured with increasing SAM concentrations to confirm its SAM competitive binding activity. D, computational docking model of JQEZ5 binding to EZH2 using reported model. E, Biacore surface plasma resonance (SPR) sensorgram from single-cycle kinetics runs with four concentrations of the PRC2 five-component complex. A biotinylated derivative of JQEZ5, JQEZ6, was immobilized on streptavidin SPR chip. The affinity (KD) of PRC2 for JQEZ6 was determined to be 87 nmol/L.
Haikuo Zhang et al. Cancer Discov 2016;6:
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