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. HTH-01-015 is a selective inhibitor of NUAK1 (IC50 = 100 nM) and does not affect the activity of a panel of 139 other kinases, including additional AMPK family members. At 10 μM, HTH-01-015 has been shown to partially inhibit the phosphorylation of the NUAK1 substrate, myosin phosphate-targeting subunit 1 at Ser445. When administered to mouse embryonic fibroblasts in vitro, 10 μM HTH-01-015 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.
HTH 01-015 is a highly specific protein kinase inhibitor of NUAK1. It inhibits the NUAK1 phosphorylation of myosin phosphate-targeting subunit 1 (MYPT1) substrate.
HTH-01-015 is a potent and selective inhibitor of NUAK1 kinase, a member of the AMPK family that are that are activated by the LKB1 (liver kinaseB1) tumour suppressor kinase and involved in development and proliferation. HTH-01-015 has an IC50 of 100 nM for NUAK1, >100-fold higher than NUAK2, and has no significant inhibition of 139 other kinases tested, including ten AMPK-related kinase family members. Treatment with HTH-01-015 was found to suppress proliferation, restricting cells from entering into mitosis.
1. sourav b, sara j b, hai-tsang h, et al. characterization of wz4003 and hth-01-015 as selective inhibitors of the lkb1-tumour-suppressor-activated nuak kinases. biochemical journal, 2014, 457(1): 215-225.
