pi4kiiibeta-in-9

Description: PI4KIIIbeta-IN-9 (PI4KIIIbeta-IN-9) is a novel, potent and selective PI4KIIIbeta (Type III phosphatidylinositol 4-kinase) inhibitor with an IC50 of 7 nM with > 1000-fold over class I and class III PI3Ks. PI4KIIIbeta-IN-9 also inhibits PI3Kdelta and PI3Kgamma with IC50s of 152 nM and 1046 nM, respectively. Type III phosphatidylinositol 4-kinase (PI4KIIIbeta) is an essential enzyme in mediating membrane trafficking and is implicated in a variety of pathogenic processes. It is a key host factor mediating replication of RNA viruses. The design of potent and specific inhibitors of this enzyme will be essential to define its cellular roles and may lead to novel antiviral therapeutics. PI4KIIIbeta-IN-9 showed antiviral activity against hepatitis C virus. The co-crystal structure of PI4KIIIbeta bound to one of PI4KIIIbeta-IN-9 reveals the molecular basis of specificity. This work will be vital in the design of novel PI4KIIIbeta inhibitors, which may play significant roles as antiviral therapeutics.

References: J Med Chem. 2016 Mar 10; 59(5):1830-9.