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.

化合物IRF1-IN-2（20 μM, 12 h）预处理能够减少辐照HaCaT细胞（20 Gy）中IRF1对CASP1启动子的招募。此外，IRF1-IN-2（20 μM, 24 h）可抑制HELF和WS1细胞内通过NSP-10质粒转染诱导的IRF1激活。IRF1-IN-2保护A375细胞免受辐射损伤（20 Gy），并阻止细胞死亡信号通路，包括抑制Caspase 1、GSDMD、IL-1和PARP1的裂解，抑制TKB1磷酸化，同时上调GPX4并下调FACL4的表达。在辐照早期阶段，IRF1-IN-2维持皮肤细胞线粒体的功能和ROS的生成。

IRF1-IN-2 预处理（100 μg/d，皮下注射，隔天照射）对35 Gy 辐射引起的炎症性皮肤损伤小鼠具有潜在的保护作用。