PD-98059 is an oxanaphthalenone-based inhibitor of MAPK-activating enzyme, MAPK/ERK kinase (MEK), without significant inhibitory activity of MAPK itself. [1] PD-98059 does not inhibit Raf-activated MAPKK1, but rather prevents activation of MAPKK1 by Raf or MEK kinase in vitro at IC50 values of 2-7 uM. [2]

Exposure of MCF10A human breast epithelial cells resulted in a rapid loss of dually phosphorylated forms of extracellular signal-regulated kinase at an IC50 of 1 uM. PD-98059 is believed to be a ligand for the aryl hydrocarbon receptor (AHR) and functions as an AHR antagonist at concentrations commonly used to inhibit MEK at the signalling processes that entail MEK activation. [3]

PD-98059 has also been shown to dramatically reduce hypoxia-induced transcription of HRE-driven reporter gene more so than that of endogenous VEGF and EPO. [4]