IRF1-IN-1 (Compound I-2) is an IRF1 inhibitor that reduces IRF1 recruitment to the CASP1 promoter. It inhibits cell death signaling pathways by preventing the cleavage of Caspase 1, GSDMD, IL-1, and PARP1. Additionally, IRF1-IN-1 has a protective effect against ionizing radiation-induced skin inflammation.

IRF1-IN-1 at a concentration of 20 μM for 12 hours reduces the recruitment of IRF1 to the CASP1 promoter in irradiated HaCaT cells (20 Gy). At 20 μM for 24 hours, IRF1-IN-1 diminishes NSP-10 plasmid-induced IRF1 activation in HELF, HaCaT, and WS1 cells. Utilizing 50 μM for 24 hours, it decreases IRF1 transcriptional activity in HELF cells 96 hours post SARS-CoV-2 pseudovirus infection. The compound reduces radiation (20 Gy)-induced K150 cell death and in the early stages post-irradiation maintains mitochondrial activity and ROS production in skin cells. IRF1-IN-1 markedly inhibits cell death signaling pathways, suppressing the cleavage of Caspase 1, GSDMD, IL-1, and PARP1.

Pre-treatment with IRF1-IN-1 (100 μg/day, subcutaneously, administered on alternate days) potentially protects mice from inflammatory skin damage induced by 35 Gy radiation.