| Description |
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[1][2][3].
|
| Related Catalog |
|
| Target |
MEK:5.7 nM (IC50)
|
| 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[1]. Zapnometinib (100 μM; 4 h) inhibits the Ionomycin (PMA/I)-induced phosphorylation of ERK1/2 in human PBMCs[1]. Zapnometinib (1-100 μM) reduces the viral titers of the IV H1N1pdm09, H3N2[1]. Western Blot Analysis[1] Cell Line: human PBMCs Concentration: 100 μM Incubation Time: 4 h Result: Inhibited the Ionomycin (PMA/I)-increased pERK1/2.
|
| 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[1]. 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[1]. Animal Model: Female C57BL/6 mice (8 weeks; 21-24 g) were infected with H1N1pdm09[1] Dosage: 8.4, 25, 75 mg/kg/day (2.8, 8.4, 25 mg/kg) Administration: P.o. three times a day Result: Significantly reduced the virus titer at the dose of either 75 mg/kg/day or 25 mg/kg/day.
|
| References |
[1]. Laure M, et, al. Antiviral efficacy against influenza virus and pharmacokinetic analysis of a novel MEK-inhibitor, ATR-002, in cell culture and in the mouse model. Antiviral Res. 2020 Jun;178:104806. [2]. Hamza H, et, al. Improved in vitro Efficacy of Baloxavir Marboxil Against Influenza A Virus Infection by Combination Treatment With the MEK Inhibitor ATR-002. Front Microbiol. 2021 Feb 12;12:611958. [3]. Bruchhagen C, et, al. Metabolic conversion of CI-1040 turns a cellular MEK-inhibitor into an antibacterial compound. Sci Rep. 2018 Jun 14;8(1):9114.
|
