Comparative Preclinical Evaluation of BIX-01294 and UNC0642 as EHMT2-Targeting Anticancer Agents

BACKGROUND: EHMT2 (G9a) is a key epigenetic regulator frequently overexpressed in various cancers. While several inhibitors exist, their in vivo efficacy and pharmacokinetic (PK) properties remain poorly characterized. METHODS: We compared the biochemical, cellular, and PK profiles of two widely used EHMT2 inhibitors, BIX-01294 and UNC0642, and evaluated their antitumor efficacy in xenograft and syngeneic mouse models. RESULTS: cells. CONCLUSIONS: These results suggest that BIX-01294 is more effective in vivo than UNC0642 due to its favorable PK profile and superior cellular uptake. Our findings support the further development of EHMT2 inhibitors as potent partners for immune checkpoint blockades.