Therapeutics: MEK

Zebrafish studies suggest MEK inhibitors could help treat anxiety caused by overactive cAMP signaling. In zebrafish larvae, a phosphodiesterase-4 (PDE-4) inhibitor promoted cAMP signaling and induced anxiety-like behaviors. Screening of 80 kinase inhibitor tool compounds in the zebrafish larva model of PDE-4 inhibitor-induced anxiety identified a MEK inhibitor that decreased anxiety-like behaviors compared with vehicle. In the zebrafish larva model and an adult zebrafish model of PDE-4 inhibitor-induced anxiety, the MEK inhibitor PD0325901 decreased anxiety-like behaviors. In normal adult zebrafish, PD0325901 did not have anxiolytic effects, whereas Buspar buspirone did. Next steps could include testing PD0325901 and other MEK inhibitors in mouse models of anxiety.

Pfizer Inc. has PD0325901, a small molecule MEK inhibitor, in Phase I testing to treat cancer...