BAY-598

BAY-598 is a **potent and selective small molecule inhibitor of SMYD2** (SET and MYND domain-containing protein 2), a lysine methyltransferase involved in the methylation of both histone and non-histone proteins, such as p53 (TP53) and RB1[3][1][5]. BAY-598 operates via a **peptide-competitive mechanism** with high selectivity (>100-fold) for SMYD2 compared to other methyltransferases[3][5]. It inhibits SMYD2 with an in vitro IC50 of 27 nM and in cells (e.g., HEK293, KYSE-150 cells) with IC50 values around 50–58 nM, efficiently reducing p53 K370 methylation[1][3][5]. BAY-598 is validated for use in both cellular and in vivo models. Mechanistic studies indicate that its antineoplastic effect may involve modulation of the JAK-STAT signaling pathway, especially when combined with doxorubicin, leading to apoptosis, cell cycle arrest, reduced invasiveness, and suppressed migration of non-small cell lung cancer (NSCLC) cells[2]. Developed by Bayer and the Structural Genomics Consortium, BAY-598 is used as a chemical probe in epigenetic and cancer research, and is available from suppliers including Sigma, Cayman Chemical, and Tocris[3][7].