ING-1466 is an orally active entry inhibitor of influenza A viruses (IAVs) with EC50 of 0.18 uM against IAV H1N1 (PR8-NS1-Gluc), binds to hemagglutinin (HA) and blocks HA-mediated viral infection.
ING-1466 has an EC50 value of 0.013 μM against pdm2009 H1N1 (A/Brownsville/39H/2009), but ING-1466 is less effective against a tissue culture adapted H1N1 PR8 virus (EC50, 3.10 μM) that has a V115M mutation in the HA2 (ATCC VR-1469).
ING-1466 shows no cytotoxicity at 100 uM in both A549 and HepG2 cells.
ING-1466 (25 and 50 mg/kg per day, i.p. or oral) produces strong inhibitory effect on infection in H1N1 mouse model.
ING-1466 alone or in combination with other drugs protects mice from IAV lethal infection.
ING-1466 has activity not only against influenza virus H1N1 (A/Puerto Rico/8/1934) but also against H5N1 (A/Vietnam/1203/2004) and the oseltamivir-resistant strains carrying NA/H274Y mutations.