BAY1238097

BAY1238097 is a potent and selective inhibitor of BET binding to histones and has strong anti-proliferative activity in different AML (acute myeloid leukemia) and MM (multiple myeloma) models through down-regulation of c-Myc levels and its downstream transcriptome (IC₅₀ <100 nM). IC50 & Target: IC50: < 100 nM (BET in a TR-FRET assay)^[1]. In Vitro: BAY 1238097 shows strong inhibitory activity (IC₅₀ < 100 nM) in a TR-FRET assay using BET BRD4 bromodomain 1 and an acetylated peptide derived from histone H4. In the NanoBRET assay, the interaction between BRD4 (IC₅₀=63 nM), BRD3 or BRD2 (IC₅₀=609 nM) and H4 (IC₅₀=2430 nM) is inhibited^[1].
BAY 1238097 has in vitro anti-tumour activity in lymphoma models. BAY 1238097 affects the gene expression of GCB DLBCL cells. At the gene level, BTK, CCDC86, CCND2, CD19, CD27, FAIM, FCMR (FAIM3), IL7R, IRAK1, MAPK13, MYB, MYC, PDE4B, TNFRSF13B, TNFRSF17 are among the top downregulated genes. Beside histone-coding genes, the upregulated genes include CCL5, CDKN2C, CD69, JUN, and MKNK2^[2]. In Vivo: BAY 1238097 shows strong efficacy in the AML and MM models. BAY 1238097 has in vivo anti-tumour activity in lymphoma models^[1][2].
BAY 1238097 is well tolerated at 10-15 mg/kg applied daily over 9-14 days in different disease models, with no obvious toxicity^[1][2].