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Overview
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Background
IC50: 25 nMVPS34-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]. In vivo: So far, there is no animal in vivo data reported. Clinical trial: Up to now, VPS34-IN1 is still in the preclinical development stage.
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- Properties
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