NIH-12848

NIH 12848 is an inhibitor of phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ; IC₅₀ = ~1 ?M).¹ It is selective for PI5P4Kγ over PI5P4Kα and PI5P4Kβ (IC₅₀s = >100 ?M). NIH 12848 inhibits translocation of the Na⁺/K⁺-ATPase to the plasma membrane in mouse principal kidney cortical collecting duct (mpkCCD) cells. NIH 12848 is also an inhibitor of USP1/UAF complex deubiquitinase activity (IC₅₀ = 7.9 ?M).² It increases accumulation of monoubiquitinated proliferating cell nuclear antigen (PCNA) in H1299 non-small cell lung cancer (NSCLC) cells when used at a concentration of 20 ?M.

1.Clarke, J.H., Giudici, M.L., Burke, J.E., et al.The function of phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ) explored using a specific inhibitor that targets the PI5P-binding siteBiochem. J.466(2)359-367(2015) 2.Dexheimer, T.S., Rosenthal, A.S., Luci, D.K., et al.Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancerJ. Med. Chem.57(19)8099-8110(2014)