In vitro activity: KIN1148 is a small-molecule agonist of the IRF3 (RIG-I-like receptor) pathway and a novel influenza vaccine adjuvant found to enhance flu vaccine efficacy. It induces the dose-dependent nuclear translocation of IRF3 in PH5CH8 cells and specific activation of IRF3- responsive promoters. KIN1148 also elicits greater induction of endogenous IRF3-dependent ISG54 and OASL expression by PH5CH8 cells. KIN1148. KIN1148 induced dose-dependent IRF3 nuclear translocation and specific activation of IRF3-responsive promoters. Prime-boost immunization of mice with a suboptimal dose of a monovalent pandemic influenza split virus H1N1 A/California/07/2009 vaccine plus KIN1148 protected against a lethal challenge with mouse-adapted influenza virus (A/California/04/2009) and induced an influenza virus-specific IL-10 and Th2 response by T cells derived from lung and lung-draining lymph nodes. Prime-boost immunization with vaccine plus KIN1148, but not prime immunization alone, induced antibodies capable of inhibiting influenza virus hemagglutinin and neutralizing viral infectivity. Nevertheless, a single immunization with vaccine plus KIN1148 provided increased protection over vaccine alone and reduced viral load in the lungs after challenge. These findings suggest that protection was at least partially mediated by a cellular immune component and that the induction of Th2 and immunoregulatory cytokines by a KIN1148-adjuvanted vaccine may be particularly beneficial for ameliorating the immunopathogenesis that is associated with influenza viruses. KIN1148 induces the dose-dependent nuclear translocation of IRF3 in PH5CH8 cells and specific activation of IRF3- responsive promoters. KIN1148 also elicits greater induction of endogenous IRF3-dependent ISG54 and OASL expression by PH5CH8 cells

Kinase Assay: KIN1148 is a small-molecule agonist of the IRF3 (RIG-I-like receptor) pathway and a novel influenza vaccine adjuvant found to enhance flu vaccine efficacy. It induces the dose-dependent nuclear translocation of IRF3 in PH5CH8 cells and specific activation of IRF3- responsive promoters. KIN1148 also elicits greater induction of endogenous IRF3-dependent ISG54 and OASL expression by PH5CH8 cells. KIN1148.

Cell Assay: KIN1148 induces the dose-dependent nuclear translocation of IRF3 in PH5CH8 cells and specific activation of IRF3- responsive promoters. KIN1148 also elicits greater induction of endogenous IRF3-dependent ISG54 and OASL expression by PH5CH8 cells.