NUAK1 (also known as AMPK-related kinase 5) and NUAK2 (also known as SNF1/AMPK-related kinase) are members of the AMP-activated protein kinase (AMPK) family of protein kinases that are activated by the liver kinase B1 tumor suppressor kinase. NUAK kinases are thought to have roles in regulating cell adhesion, cancer cell invasion, embryonic development, senescence, proliferation, neuronal polarity, and axon branching. WZ4003 is a selective inhibitor of NUAK1 and NUAK2 (IC50s = 20 and 100 nM, respectively). It does not affect the activity of a panel of 139 other kinases, including additional AMPK family members. At 3-10 μM, WZ4003 has been shown to inhibit the phosphorylation of the NUAK1 substrate, myosin phosphate-targeting subunit 1 at Ser445. When administered to mouse embryonic fibroblasts in vitro, 10 μM WZ4003 inhibits proliferation and migration in a wound-healing assay. It has also been shown to impair the invasive potential of U2OS cells at similar concentrations in a 3D cell invasion assay.
