PD 98059

PD 98059 is a noncompetitive inhibitor of the MAPK pathway.^1,2 It prevents the activation of MEK by Raf or MEK kinase (a MAP3K) with an IC₅₀ value of 2-7 µM but does not inhibit Raf-activated MAP2K1.³ It inhibits Raf activation of MAP2K2 with an IC₅₀ value of 50 µM.³ PD 98059 also phosphorylates and activates AMP-activated protein kinase (AMPK) in a dose-dependent manner (EC₅₀ = 35 µM in HEK293 cells).⁴ It increases the ratios of ADP to ATP and AMP to ATP and increases phosphorylation of the AMPK target acetyl-CoA carboxylase (ACC).

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1. Davies, S.P., Reddy, H., Caivano, M., et al. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351(1), 95-105 (2000).

2. Dudley, D.T., Pang, L., Decker, S.J., et al. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc. Natl. Acad. Sci. USA 92(17), 7686-7689 (1995).

3. Alessi, D.R., Cuenda, A., Cohen, P., et al. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. The Journal of Biological Chemisty 270(46), 27489-27494 (1995).

4. Dokladda, K., Green, K.A., Pan, D.A., et al. PD98059 and U0126 activate AMP-activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway. FEBS Lett. 579(1), 236-240 (2005).

Yousefi, B., Azimi, A., Majidinia, M., et al. Balaglitazone reverses P-glycoprotein-mediated multidrug resistance via upregulation of PTEN in a PPARγ-dependent manner in leukemia cells. Tumour Biol. 39(10), (2017).

Arai, T., Ono, Y., Arimura, Y., et al. Type I neuregulin1α is a novel local mediator to suppress hepatic gluconeogenesis in mice. Sci. Rep. 7, 42959 (2017).