AC-45594

AC-45594 is a UPR activator. It induces endoplasmic reticulum stress and activates the unfolded protein response (UPR), promoting the shift from adaptive to terminal stress signaling, ultimately leading to apoptosis (Apoptosis). AC-45594 activates Caspase-3, induces PARP cleavage, and increases DR5 protein levels, selectively inhibiting the growth of Ewing sarcoma cells.

AC-45594 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 over 72 hours, with EC50 values ranging from 45.0 ± 2.2 to 144.3 ± 13.0 nM. At concentrations of 25-200 nM over 72 hours, AC-45594 induces apoptosis in SK-ES-1 and TC-71 Ewing sarcoma cell lines, reducing cell populations in both the S phase and G2/M phase. Additionally, at 200 nM for 8-16 hours, AC-45594 triggers a sequential activation of unfolded protein response and pro-apoptotic signaling in SK-ES-1 Ewing sarcoma cells, with early stress response changes observed at 8 hours and extensive UPR activation and initiation of apoptosis at 16 hours.