PIK-93

PIK-93 is the first potent, synthetic PI4K (PI4KIIIβ) inhibitor with IC₅₀ of 19 nM, and also inhibits PI3Kγ and PI3Kα with IC₅₀ of 16 nM and 39 nM, respectively. IC50 & Target: IC50: 19 nM (PI4KIIIβ), 39 nM (p110α), 16 nM (p110γ), 590 nM (p110β), 120 nM (p110δ), 140 nM (PI3KC2β), 64 nM (DNA-PK)^[1] In Vitro: PIK-93 inhibits PI3Kγ and PI4KIIIβ, with IC₅₀ values of 16 nM and 19 nM, respectively. PIK-93 also inhibits other members of PI3Ks, including PI3Kα, β, and δ, with IC₅₀ values of 39 nM, 0.59 μM, and 0.12 μM, respectively. PIK-93 shows no obvious inhibitory effect against a panel of other kinases, even at a concentration of 10 μM^[1]. In differentiated HL60 (dHL60) cells, PIK-93 (0.5 μM-1 μM) impairs consolidation and stability of the leading edge formed after treatment with uniform f-Met-Leu-Phe (fMLP). PIK-93 alters the localization, but not the amount, of the fMLP-dependent accumulation of total F-actin. In fMLP gradients, PIK-93 reduces the chemotactic index and triples the cells' turning frequency^[2]. In COS-7 cells, PIK-93 (250 nM) effectively abrogates the accumulation of CERT-PH domain and FL-Cer in Golgi. PIK-93 of the same concentration also significantly inhibits the conversion of [³H]serine-labeled endogenous ceramide to sphingomyelin. These facts indicate a key role of PI4KIIIβ in ceramide transport between the ER and Golgi, as well as in the regulation of spingomyelin synthesis^[3]. In T6.11 cells, PIK-93 (300 nM) reduces carbachol-induced translocation of TRPC6 to the plasma membrane and net Ca²⁺ entry^[4]. A recent report shows that PIK-93 has anti-enterovirus effects, as revealed by its inhibition of both poliovirus (PV) and hepatitis C virus (HCV) replication, with EC₅₀ values of 0.14 µM and 1.9 µM, respectively^[5].