VPS34 inhibitor 1 (Compound 19, PIK-III analogue)

Catalog No.S8456

VPS34 inhibitor 1 (Compound 19, PIK-III analogue) Chemical Structure

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.

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Biological Activity

Description VPS34 inhibitor 1 (Compound 19, PIK-III analogue) is a potent and selective inhibitor of VPS34 with an IC50 of 15 nM.
Targets
VPS34 [1]
(Cell-free assay)
15 nM
In vitro

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[1].

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[1].

Protocol

Cell Research:[1]
+ Expand
  • Cell lines: U2OS cells
  • Concentrations: 0, 1, 5, 10 μM
  • Incubation Time: 24 h
  • Method: For inhibitor assay, cells are plated and the following day when cells had reached 90%, are treated with dimethyl sulfoxide (DMSO, vehicle) or the indicated concentration of PIK-III or Compound 19, both dissolved in DMSO. 24 hours later, cells are lysed in RIPA supplemented with 1% SDS and mini-EDTA protease inhibitors, homogenized by passage through a Qiashredder column and the protein is quantified by DC Lowry protein assay.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: C57BL/6 Mice
  • Formulation: PG (20% v/v)
  • Dosages: 10 mg/kg(p.o.) or 2 mg/kg(I.V.)
  • Administration: oral administration or I.V.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 78 mg/mL (199.24 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 391.47
Formula

C21H25N7O

CAS No. 1383716-46-8
Storage powder
in solvent
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID