IRF1-IN-2 (Compound I-19) is an IRF1 inhibitor. IRF1-IN-2 reduces the recruitment of IRF1 to the CASP1 promoter. IRF1-IN-2 inhibits cell death signaling pathways (i.e., inhibits the cleavage of Caspase 1, GSDMD, IL-1, and PARP1; inhibits the phosphorylation of TKB1, upregulates GPX4, and downregulates FACL4). IRF1-IN-2 has a protective effect against ionizing radiation-induced skin inflammatory damage.

Physicochemical Properties

Molecular Formula	C18H20N2O4S
Molecular Weight	360.43
CAS #	708245-32-3
Appearance	White to off-white solid powder
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	PARP-1 IL-1 Caspase-1
ln Vitro	Pretreatment with IRF1-IN-2 (20 μM, 12 h) reduces the recruitment of IRF1 to the CASP1 promoter in irradiated HaCaT cells (20 Gy) [1]. IRF1-IN-2 (20 μM, 24 h) attenuates IRF1 activation induced by NSP-10 plasmid transfection in HELF and WS1 cells [1]. IRF1-IN-2 protects A375 cells from radiation (20 Gy) [1]. IRF1-IN-2 inhibits cell death signaling pathways, including inhibition of Caspase 1, GSDMD, IL-1 and PARP1 cleavage, TKB1 phosphorylation, upregulation of GPX4 and downregulation of FACL4 [1]. IRF1-IN-2 maintains mitochondrial activity and ROS production in skin cells in the early stages after irradiation [1].
ln Vivo	IRF1-IN-2 pretreatment (100 μg/d, subcutaneous injection, irradiation every other day) has a potential protective effect against inflammatory skin damage induced by 35 Gy radiation in mice [1].
Animal Protocol	Animal/Disease Models: Radiogenic skin injury mice (intraperitoneal injection of pentobarbital sodium (1%, 30 mg/kg), 35 Gy at the dose rate of 1000 cGy/min by a 6-MeV electron beam)[1] Doses: 100 μg/d Route of Administration: Subcutaneous injection (s.c.), one every other day before irradiation, pretreatment Experimental Results: Showed a significant reduction in acute skin inflammatory manifestations, such as erythema and exudation. Showed protective effects on the function and structural integrity of radiation-induced lesions to the claws.
References	[1]. 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.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~346.81 mM; with ultrasonication)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7745 mL	13.8723 mL	27.7446 mL
	5 mM	0.5549 mL	2.7745 mL	5.5489 mL
	10 mM	0.2774 mL	1.3872 mL	2.7745 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.