RO8191 is an orally active interferon (IFN) receptor agonist that displays potent anti-Hepatitis C virus (HCV) activity with an EC50 value of 0.2µM[1]. RO8191 activates the JAK2/STAT3 signaling pathway, reducing the protein density of E-cadherin and promoting the process of epithelial-mesenchymal transition (EMT)[2]. RO8191 has been widely used in tumor research to regulate the malignant phenotype of non-small cell lung cancer and the tumor microenvironment[3].
In vitro, RO8191 treatment for 16 hours significantly inhibited the replication of Chikungunya virus (CHIKV) in BHK-21 cells, with an EC50 value of 0.88µM[4]. 4µM of RO8191 treatment for 24 hours interfered with the inhibitory effect of 25µM Baicalein on the expression of p-STAT3, c-Myc and GLUT1 in lipopolysaccharide (LPS)-treated BV-2 cells, and restored glycolytic activity[5]. Treatment with 10µM RO8191 for 7 days reversed the inhibitory effect of si-FoxO1 on the cell death of SRA01/04 cells under high glucose conditions, reducing cell viability and increasing the expression levels of NLRC4 and IL-6[6]. Incubation with 10µM RO8191 for 48 hours reversed the cell death and pyroptosis mediated by SH-4-54 (10µM) in U87 and LN229 cells, and restored the normal morphology of the cells[7].
In vivo, a single intraperitoneal injection of RO8191 at a dose of 400µg on the third day induced embryo implantation and decidualization in a mouse model of delayed implantation, and activated STAT3 in the endometrium[8]. Intraperitoneal injection of RO8191 at a dose of 1mg/kg/day for 5 consecutive days aggravated radiation-induced esophagitis, reduced the area of the epithelial layer, increased the mRNA levels of Cxcl1 and Il1b in esophageal tissue, accompanied by elevated levels of cleaved PARP protein, and led to body weight loss in mice[9].
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[2] Lei H, Shi J, Teng Y, et al. Baicalein modulates the radiosensitivity of cervical cancer cells in vitro via miR-183 and the JAK2/STAT3 signaling pathway[J]. Advances in Clinical and Experimental Medicine, 2021, 30(7): 727-736.
[3] Shi S, Han J, Wu Q, et al. FAM64A regulates the malignant phenotype and tumor microenvironment of non-small cell lung cancer by activating the JAK/STAT3/PDL1 axis[J]. Journal of Molecular Histology, 2025, 56(2): 95.
[4] Ruiz U E A, Santos I A, Grosche V R, et al. Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways[J]. Virus Research, 2023, 324: 199029.
[5] Gao L, Liu Y, Zhou Y, et al. Baicalein attenuates neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis via STAT3/c-Myc pathway[J]. Neurochemical Research, 2023, 48(11): 3363-3377.
[6] Li Y, Pan A P, Ye Y, et al. FoxO1 promotes high glucose-induced inflammation and cataract formation via JAK1/STAT1[J]. Graefe's Archive for Clinical and Experimental Ophthalmology, 2025, 263(6): 1585-1596.
[7] Yu D, Wang S, Wang J, et al. EZH2–STAT3 signaling pathway regulates GSDMD-mediated pyroptosis in glioblastoma[J]. Cell Death Discovery, 2024, 10(1): 341.
[8] Shu J, Terakawa J, Takikawa S, et al. RO8191, a new compound for initiating embryo implantation in mice[J]. Scientific Reports, 2025, 15(1): 32387.
[9] Kitamura H, Tanigawa T, Kuzumoto T, et al. Interferon-α exerts proinflammatory properties in experimental radiation-induced esophagitis: possible involvement of plasmacytoid dendritic cells[J]. Life sciences, 2022, 289: 120215.