SAR405,1523406-39-4,IC-0202982

SAR405 is a Vps34 inhibitor (IC50=1.2 nM),SAR405 inhibits autophagy caused by mTOR inhibition[1，2].
Treatment of RKO colorectal cancer cells with SAR405 showed large translucent vacuoles 16 h after treatment with SAR405 at 10 μM. These vacuoles were positive for the lysosomotropic dye Lysotracker and were also decorated with the lysosomal membrane protein Lamp1[1]. Under normal growth conditions, the GFP-FYVE probe appeared as green spots,This relocalization of the GFP-FYVE indicated that SAR405 inhibits PtdIns3P formation. By quantifying the positive cells, it can determine an IC50 of 27 nM[1]. Inhibition of autophagy by SAR405, in general, or of the autophagy-inducing class III PtdIns3K complex, in particular, sensitized both sensitive and resistant urothelial carcinoma cells to cisplatin-induced cytotoxic effects[3]. Chromosome missegregation induced by reverse transcriptase can produce excess protein subunit protein complex imbalance proteotoxic stress and autophagy activation, which may contribute to the removal of misfolded or redundant proteins, afA and SAR405 reverse the reverse-dependent nuclear phagocytosis flux[4]. Actin domain formation was repressed by the depletion of PI3P by SAR405, an inhibitor of the class III PI3 kinase, Vps34, and by the use of diabetic model cells, in which PI3P was depleted. SAR405 did not affect the phosphorylation level of Akt, and the transcriptional regulation of gluconeogenic and cholesterol synthetic genes after insulin treatment[6]. Deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-β1, induced fibroblast activation and senescence: In response to TGF-β1, autophagy was induced prior to the development of the activated and senescent phenotypes[7].
Local delivery of SAR405 to the BLA impaired freezing behaviors at 24 hours, with no difference was observed at 3 hours. In addition, SAR405 administation had no effect on memory retrival test[5].