EU-5346 (ML311) is a small molecule Mcl-1 inhibitor with IC50 of 0.31 uM, potently and selectively disrupts Mcl-1/Bim interaction.
EU-5346 induced cell death and decreased spheroid formation in Her2-positive BC cells.
EU-5346 induced ubiquitination of Mcl-1- bound Her2 demonstrating a previously unknown role for Mcl-1 to stabilize Her2 protein levels.
When combined with tamoxifen or trastuzumab, EU-5346 induced significant anti-BC activity in hormone receptor positive or Her2-positive BC cells, respectively.
EU-5346 in combination with paclitaxel induced synergistic anti-BC activity in both paclitaxel-sensitive and paclitaxel-resistant TNBC cells.
