IRF1-IN-1 (Compound I-2) is an IRF1 inhibitor that reduces IRF1 recruitment to the Caspase 1 promoter, inhibiting the cleavage of Caspase 1, GSDMD, IL-1, and PARP1, thereby protecting against skin inflammatory damage.

Method:
Various cell models (HELF, HaCaT, WS1, and K150) were treated with IRF1-IN-1 at concentrations ranging from 20 to 50 μM. The effects were evaluated under conditions such as irradiation (20 Gy), NSP-10 plasmid transfection, or SARS-CoV-2 pseudovirus infection to assess IRF1 activity, cell death-related signaling, and mitochondrial function.

Result:
IRF1-IN-1 inhibited IRF1-mediated transcriptional regulation of downstream genes (e.g., CASP1), reduced IRF1 activation induced by NSP-10 or viral infection, alleviated radiation-induced cell death, maintained mitochondrial activity and ROS levels, and significantly suppressed the cleavage of Caspase 1, GSDMD, IL-1, and PARP1, demonstrating a strong cytoprotective effect. [1]

Method:
A radiogenic skin injury mouse model was established using whole-body irradiation with a 6-MeV electron beam at a dose of 35 Gy and a dose rate of 1000 cGy/min. Mice were anesthetized prior to irradiation with an intraperitoneal injection of pentobarbital sodium (1%, 30 mg/kg). IRF1-IN-1 was administered subcutaneously at a dose of 100 μg/day, once every other day as a pretreatment before irradiation.

Result:
IRF1-IN-1 significantly reduced acute skin inflammatory manifestations such as erythema and exudation, and accelerated the healing process. It also exhibited protective effects on the function and structural integrity of radiation-induced lesions in the claws. [1]