VPS34 inhibitor 1 (Compound 19, PIK-III analogue)
Molecular Weight(MW): 391.47
VPS34 inhibitor 1 (Compound 19, PIK-III analogue) is a potent and selective inhibitor of VPS34 with an IC50 of 15 nM.
1 Customer Review
Confirmation of selective growth inhibition using VPS34-IN1 inhibitor. Proliferation of Tsc2+/+ and Tsc2-/- MEFs treated with vehicle control (DMSO), CQ (5 uM), VPS34-IN1 (500 nM) or the combination for 72 hours (crystal violet staining). Two sample t-test was carried out between CQ and SAR405 and each drug alone. Results are representative of three independent experiments. Bar graph represent means ±SD.
Oncotarget, 2017, 8(24):38099-38112. VPS34 inhibitor 1 (Compound 19, PIK-III analogue) purchased from Selleck.
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|Description||VPS34 inhibitor 1 (Compound 19, PIK-III analogue) is a potent and selective inhibitor of VPS34 with an IC50 of 15 nM.|
Compound 19 is extraordinarily selective over other lipid and protein kinases. The ability of compound 19 to prevent the degradation of autophagy substrates p62, NCOA4, NBR1, NDP52, and FTH1 is similar to PIK-III. In addition, treatment of cells with compound 19 leads to an increase in the lipidated and nonlipidated forms of LC3 similar to previous reports using PIK-III.
|In vivo||The pharmacokinetic profile of analogue 19 is determined in C57BL/6 mice. After oral administration at 10 mg/kg, the compound is rapidly absorbed and showed moderate mean systemic clearance (30 mL/min/kg, approximately 33% of hepatic blood flow), with good oral bioavailability (F% = 47). Based on these PK parameters and the cellular activity, compound 19 constitutes a suitable candidate for in vivo studies. Upon oral administration of compound 19 at 50 mg/kg twice a day (BID) for 7 days, LC3-II accumulates consistent with reduced autophagic capacity in time-dependent manner. It inhibits autophagy in vivo.|
|In vitro||DMSO||78 mg/mL (199.24 mM)|
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