Vps34-IN-1

The Uses of Vps34-IN-1

Vps34-IN-1 is a potent and selective inhibitor of phosphoinositide 3-kinase (PI3K) vacuolar protein sorting 34 (VPS34) (1). VPS34 inhibitors can be used to investigate autophagic processes (2).

Biological Activity

vps34-in1 is a vps34 inhibitor.the vacuolar protein sorting 34 (vps34) class iii phosphoinositide 3-kinase (pi3k) phosphorylates phosphatidylinositol (ptdins) to generate ptdins(3)p that regulates membrane trafficking processes through its ability to recruit a subset of proteins possessing ptdins(3)p-binding phox homology (px) and fyve domains.

in vitro

vps34-in1 was identified to be able to inhibit in-vitro vps34, but did not significantly inhibit the activity of tested 340 protein kinases or 25 lipid kinases that include all isoforms of class i and class ii pi3ks. treatment of vps34-in1 to cells dose-dependently induced a quick dispersal of a specific ptdins(3)p-binding probe, without altering the ability of class i pi3k to regulate akt. moreover, vps34-in1 could also induce a quick ~50-60% loss of sgk3 phosphorylation within 1 min. however, vps34-in1 could not inhibit activity of the sgk2 isoform without a ptdins(3)p-binding px domain. in addition, the combination of vps34-in1 and class i pi3k inhibitor of gdc-0941 resulted in the reduced sgk3 activity ~80-90%. therefore, these data demonstrated that vps34-in1 would be a useful probe to delineate physiological roles of the vps34 and the combination of class i such as gdc-0941 and class iii such as vps34-in1 pi3k inhibitors could be used to better analyse the roles and regulation of the elusive class ii pi3k [1].

References

[1] bago r et al. characterization of vps34-in1, a selective inhibitor of vps34, reveals that the phosphatidylinositol 3-phosphate-binding sgk3 protein kinase is a downstream target of class iii phosphoinositide 3-kinase. biochem j.2014 nov 1;463(3):413-27.