The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi.In mammals there are four different PI4K enzymes, two type II enzymes (PI4KIIα and PI4KIIβ) and two type III enzymes (PI4KIIIα and PI4KIIIβ). PI4KIIIβ plays key roles in mediating lipid transport, cytokinesis, maintaining lysosomal identity, and in tandem with Rab GTPases plays key roles in regulating membrane trafficking. PI4KIIIβ is critical for mediating viral replication of a number of RNA viruses through the generation of PI4P enriched viral replication platforms. Small molecule inhibitors of PI4KIIIβ are potent anti-viral agents. Development of PI4KIIIβ as an effective drug target for anti-viral therapeutics requires the generation of highly potent and specific inhibitors.
||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.
||PI4KIII beta inhibitor 3
||PI4KIII beta inhibitor 3 is a novel and high effective ΡΙ4ΚΙΙΙβ inhibitor with IC50 of 5.7 nM.
||PI4KIIIbeta-IN-9 is a potent PI4KIIIβ inhibitor with an IC50 of 7 nM. PI4KIIIbeta-IN-9 also inhibits PI3Kδ and PI3Kγ with IC50s of 152 nM and 1046 nM, respectively.
||BQR-695 is a PI4KIIIβ inhibitor with IC50s of 80 and 3.5 nM for human PI4KIIIβ and Plasmodium variant of PI4KIIIβ, respectively.
||KDU691 is a PI4K inhibitor.
||MMV390048 is a novel potent Plasmodium PI4K inhibitor with IC50 of 28 nM against intraerythrocytic life cycle stages of P. falciparum (NF54 drug-sensitive strain).