AC-45594

AC-45594 is a UPR activator. AC-45594 induces endoplasmic reticulum stress, activates the unfolded protein response (UPR), and drives the transition from adaptive stress signaling to terminal stress signaling, ultimately leading to cell Apoptosis. AC-45594 activates Caspase-3, induces PARP cleavage, and increases the protein level of DR5. AC-45594 selectively inhibits the growth of Ewing sarcoma cells^[1]. In Vitro:AC-45594 (72 h) selectively inhibits the growth of Ewing sarcoma cell lines COG-E-352, SK-ES-1, TC-32, SKNMC, TC-71 and TC-106 in a concentration-dependent manner, with EC₅₀ values ranging from 45.0 ± 2.2 to 144.3 ± 13.0 nM^[1].
AC-45594 (25-200 nM; 72 h) induces apoptosis in SK-ES-1 and TC-71 Ewing sarcoma cell lines, while reducing the cell populations in the S and G₂/M phases^[1].
AC-45594 (200 nM; 8-16 h) triggers sequential activation of the unfolded protein response and pro-apoptotic signaling in SK-ES-1 Ewing sarcoma cells, with early stress response changes observed at 8 h post-treatment, and extensive UPR activation and apoptosis initiation detected at 16 h post-treatment^[1].