IRF1-IN-2 (Compound I-19) is an inhibitor of IRF1. It reduces the recruitment of IRF1 to the CASP1 promoter and hinders cell death signaling pathways by inhibiting the cleavage of Caspase 1, GSDMD, IL-1, and PARP1, as well as by preventing the phosphorylation of TKB1. The compound also upregulates GPX4 and downregulates FACL4. Additionally, IRF1-IN-2 provides protective effects against skin inflammatory damage induced by ionizing radiation.

IRF1-IN-2, at a concentration of 20 μM for 12 hours, reduces the recruitment of IRF1 to the CASP1 promoter in irradiated HaCaT cells (20 Gy). Additionally, IRF1-IN-2, at 20 μM for 24 hours, diminishes IRF1 activation induced by NSP-10 plasmid transfection in HELF and WS1 cells. The compound also offers protection for A375 cells against radiation (20 Gy). It inhibits cell death signaling pathways, including suppression of Caspase 1, GSDMD, IL-1, and PARP1 cleavage, phosphorylation of TKB1, upregulation of GPX4, and downregulation of FACL4. Moreover, IRF1-IN-2 maintains the activity of mitochondria and the production of ROS in skin cells at the early stages post-irradiation.

IRF1-IN-2 pre-treatment (100 μg/day, subcutaneous injection, administered every other day) may offer potential protective effects against inflammatory skin damage in mice induced by 35 Gy radiation.