Background:

PIK-93 is a potent and novel inhibitor of p110γ (PI3Kγ) and PI4KIIIβ (IC50= 16 nM and 19 nM, respectively).

PI3K (phosphatidylinositol-4,5-bisphosphate 3-kinase) is a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. It plays a key role in PI3K/Akt/mTOR pathway.

Inhibition of PI3K via PIK-93 reduced the carbachol-activated translocation of TRPC6 to the plasma membrane and carbachol-activated net Ca(2+) entry into T6.11 cells. [1] PIK-93 also selectively inhibited the PI4KIIIβ enzyme, and siRNA-mediated down regulation of individual PI4-enzymes in COS-7 cells. [2] Furthermore, as a potent anti-PV compound, PIK93 targeted PI4Kβ to inhibit interaction of viral 3D polymerase and phosphatidylinositol 4-phosphate on the reorganized membrane vesicle for viral replication complex formation. [3] PIK93 also showed anti-PV with an EC50 of 0.14 μM for PV pseudovirus infection. [4]

参考文献:
[1] Monet M, Francoeur N, Boulay G.  Involvement of phosphoinositide 3-kinase and PTEN protein in mechanism of activation of TRPC6 protein in vascular smooth muscle cells.  J Biol Chem. 2012 May 18;287(21):17672-81.
[2] Tóth B, Balla A, Ma H et al.  Phosphatidylinositol 4-kinase IIIbeta regulates the transport of ceramide between the endoplasmic reticulum and Golgi. J Biol Chem. 2006 Nov 24;281(47):36369-77.
[3] Hsu, N.  Y., et al. 2010. Viral reorganization of the secretory pathway generates distinct organelles for RNA replication.  Cell 141:799-811.
[4] Arita M, Kojima H, Nagano T et al.  Phosphatidylinositol 4-kinase III beta is a target of enviroxime-like compounds for antipoliovirus activity. J Virol. 2011 Mar;85(5):2364-72.