EPZ020411

EPZ020411 is a potent and selective small molecule inhibitor of protein arginine methyltransferase 6 (PRMT6), with an IC50 of 10 nM and over tenfold selectivity for PRMT6 compared to PRMT1 and PRMT8. As the first tool compound developed for selective inhibition of PRMT6, it has been widely used in preclinical research to study the biological functions of this enzyme. Mechanistically, EPZ020411 inhibits the methylation activity of PRMT6, which plays a key role in post-translational modification affecting RNA processing, transcriptional regulation, and signal transduction. In cancer models—particularly mismatch repair-proficient (MSS) colorectal cancer—EPZ020411 enhances immune checkpoint blockade efficacy by activating cGAS-STING signaling through disruption of MMR capacity via inhibition of MSH2 dimethylation. The compound demonstrates good bioavailability following subcutaneous dosing in animal studies but remains at the preclinical development stage[1][2][4][5][6].