YM458

YM458 is a first-in-class **dual small molecule inhibitor** targeting both **EZH2 (Histone-lysine N-methyltransferase EZH2)** and **BRD4 (Bromodomain-containing protein 4)**[1][3][5][9]. It displays potent inhibitory activity with IC50 values of 490 nM for EZH2 and 34 nM for BRD4[3]. YM458 reduces the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl, reverses H3K27 acetylation, and increases p21 expression, contributing to antiproliferative effects in cancer cells[5]. It demonstrates strong antitumor activity against 11 solid cancer cell lines and shows in vivo efficacy in lung and pancreatic cancer xenograft mouse models[9]. The drug was designed to overcome resistance mechanisms seen in solid tumors treated with EZH2 inhibitors alone[1][5][9].

Other names

YM458YM-458YM 458