[CAS NO. 1383716-46-8] VPS34 inhibitor 1 (Compound 19)
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PRODUCTS SPECIFICATIONS [1383716-46-8]
Store
Catalog
SLK-S8456
Brand
Selleck
CAS
1383716-46-8
DESCRIPTION [1383716-46-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 391.47 |
| Molecular Formula | C21H25N7O |
| SMILES | CC(O)(C)CNC1=NC=C(C2=NC(NC3=CC=NC=C3)=NC=C2)C(CC4CC4)=N1 |
For research use only.
Storage
3 years,-20°C,powder
1 years,-80°C,in solvent
1 years,-80°C,in solvent
Shipping
Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)
Preparing Stock Solutions
| 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5545 mL | 12.7724 mL | 25.5447 mL |
| 5 mM | 0.5109 mL | 2.5545 mL | 5.1089 mL |
| 10 mM | 0.2554 mL | 1.2772 mL | 2.5545 mL |
| 50 mM | 0.0511 mL | 0.2554 mL | 0.5109 mL |
Description
VPS34 inhibitor 1 (Compound 19, PIK-III analogue) is a potent and selective inhibitor of 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.
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.
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