Zapnometinib (PD0184264), an active metabolite of CI-1040, is a MEK inhibitor, with an IC50 of 5.7 nM. Zapnometinib exhibits antiviral activity against influenza virus and antibacterial activities[2].In Vitro: Zapnometinib (0.1 nM-1 μM) inhibits MEK, with IC50s of 30.96 nM, 357 nM, and 15 nM in cell free kinase assay, A549, MDCK cells and human PBMCs.
Zapnometinib (100 μM; 4 h) inhibits the Ionomycin (PMA/I)-induced phosphorylation of ERK1/2 in human PBMCs.
Zapnometinib (1-100 μM) reduces the viral titers of the IV H1N1pdm09, H3N2.In Vivo: Zapnometinib (8.4-75 mg/kg/day; three times a day p.o.) reduces the lung virus titers and enhances survival of mice after lethal H1N1pdm09 infection.
Zapnometinib (150 mg/kg) exhibits AUC values of 860.02 and 1953.68 μg?h/mL in mice by i.v. or oral route, respectively.