IRF1-IN-2

IRF1-IN-2 (Compound I-19) is an IRF1 inhibitor. IRF1-IN-2 decreases the recruitment of IRF1 to the promoter of CASP1. IRF1-IN-2 inhibits cell death signaling pathway (i.e., cleavage of Caspase 1, GSDMD, IL-1 and PARP1; inhibits the Pho of TKB1, upregulates GPX4 and downregulates FACL4). IRF1-IN-2 has a protective effect on ionizing radiation-induced inflammatory skin injury ^[1].

In Vivo, IRF1-IN-2 pretreatment (100 μg/d, s.c., one every other day before irradiation) has a potential protective effect in 35 Gy radiation-induced inflammatory skin injury mice^[1].

In Vitro, IRF1-IN-2 pretreatment (20 μM, 12 h) decreases the recruitment of IRF1 to the promoter of CASP1 in irradiated HaCaT cells (20 Gy)^[1]. IRF1-IN-2 (20 μM, 24 h) attenuates the NSP-10 plasmid transfection-induced IRF1 activation in HELF and WS1 cells^[1]. IRF1-IN-2 protects A375 cells against radiation (20 Gy)^[1]. IRF1-IN-2 inhibits cell death signaling pathways, including inhibition of cleavage for Caspase 1, GSDMD, IL-1 and PARP1, phosphorylation of TKB1, up-regulation of GPX4 and down-regulation of FACL4^[1]. IRF1-IN-2 maintains mitochondrial activity and ROS production in skin cells in the early stage after irradiation^[1].

References:
[1]. Geng, et al. Chaperone- and PTM-mediated activation of IRF1 tames radiation-induced cell death and the inflammatory response. Cell Mol Immunol. 2024 Aug;21(8):856-872.