HTH-01-015

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.Formal Name: 5,13-dihydro-4,5,13-trimethyl-2-[[1-(4-piperidinyl)-1H-pyrazol-4-yl]amino]-6H-naphtho[2,3-e]pyrimido[5,4-b][1,4]diazepin-6-one. CAS Number: 1613724-42-7. Molecular Formula: C26H28N8O. Formula Weight: 468.6. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml, Ethanol: 20 mg/ml. lambdamax: 228, 254 nm. SMILES: CC1=C(N(C)C(C2=CC(C=CC=C3)=C3C=C2N4C)=O)C4=NC(NC5=CN(N=C5)C6CCNCC6)=N1. InChi Code: InChI=1S/C26H28N8O/c1-16-23-24(31-26(29-16)30-19-14-28-34(15-19)20-8-10-27-11-9-20)32(2)22-13-18-7-5-4-6-17(18)12-21(22)25(35)33(23)3/h4-7,12-15,20,27H,8-11H2,1-3H3,(H,29,30,31). InChi Key: CHSDJDLAKKAWCI-UHFFFAOYSA-N.