PIK-III

Catalog No.S7683 Batch:S768301

Technical Data

Formula	C₁₇H₁₇N₇
Molecular Weight	319.36	CAS No.	1383716-40-2
Solubility (25°C)*	In vitro	DMSO	63 mg/mL (197.26 mM)
		Ethanol	63 mg/mL (197.26 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or 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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

PIK-III (VPS34-IN2), which is a selective inhibitor of VPS34 enzymatic activity, inhibits autophagy and de novo lipidation of LC3 and leads to the stabilization of autophagy substrates. The IC50 values for VPS34 and PI(3)Kδ are 0.018 μM and 1.2 μM respectively.

Targets

Vps34 ^[1] (Cell-free assay)	PI3Kδ ^[1] (Cell-free assay)
0.018μM	1.2μM

In vitro

VPS34 enzymatic function is essential for LC3 lipidation in mammalian cells and PIK-III is a robust inhibitor of autophagy and LC3 lipidation in mammalian cells. In H4 cells, PIK-III inhibits the formation of autolysosomes and increases the cytosolic signal of LC3 under basal conditions and when autophagy is induced with the mTOR inhibitor AZD8055. In a CCCP-induced mitophagy model, PIK-III inhibits the clearance of mitochondria.PIK-III treatment leads to an increase in the levels of LC3-I in H4 and PSN1 cells. In Panc10.05 cells, PIK-III increases the levels of LC3-II in parallel with LC3-I suggesting a cell type-specific response^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines H4 cells/ HeLa cells Concentrations 2.5μM in H4 cells/5μM in Hela cells Incubation Time overnight for H4 cells/12h for Hela cells Method To determine whether inhibition of VPS34 function impacts autophagy，LC3 and known autophagy substrates such as damaged mitochondria or the autophagy cargo receptor p62 are monitored. H4 cells expressing mCherry–GFP–LC3 are treated overnight with the indicated compounds, fixed, stained with Hoechst 33342 and imaged by automated acquisition. HeLa cells expressing GFP–Parkin are treated with PIK-III for 12 h followed by the addition of CCCP for 12 h, fixed, stained for endogenous Tom20 and imaged.

Cell Assay:^{^[1]}

Cell lines
H4 cells/ HeLa cells
Concentrations
2.5μM in H4 cells/5μM in Hela cells
Incubation Time
overnight for H4 cells/12h for Hela cells
Method
To determine whether inhibition of VPS34 function impacts autophagy，LC3 and known autophagy substrates such as damaged mitochondria or the autophagy cargo receptor p62 are monitored. H4 cells expressing mCherry–GFP–LC3 are treated overnight with the indicated compounds, fixed, stained with Hoechst 33342 and imaged by automated acquisition. HeLa cells expressing GFP–Parkin are treated with PIK-III for 12 h followed by the addition of CCCP for 12 h, fixed, stained for endogenous Tom20 and imaged.

References

[1] Dowdle WE, et al. Nat Cell Biol. 2014, 16(11):1069-1079.

Customer Product Validation

: , , molecular biosystems, 2017, 13(10):1993-2005

Selleck's PIK-III has been cited by 21 publications

Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression [ Cell Rep, 2024, 43(1):113575]	PubMed: 38181788
Targeting autophagy as a therapeutic strategy in pediatric acute lymphoblastic leukemia [ Sci Rep, 2024, 14(1):4000]	PubMed: 38369625
Crucial role of iron in epigenetic rewriting during adipocyte differentiation mediated by JMJD1A and TET2 activity [ Nucleic Acids Res, 2023, gkad342]	PubMed: 37158274
A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their disease-associated regulation [ Nat Commun, 2022, 13(1):83]	PubMed: 35013169
Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy [ Cell Death Dis, 2022, 13(4):398]	PubMed: 35459212
Autophagy Targeting and Hematological Mobilization in FLT3-ITD Acute Myeloid Leukemia Decrease Repopulating Capacity and Relapse by Inducing Apoptosis of Committed Leukemic Cells [ Cancers (Basel), 2022, 14(2)453]	PubMed: 35053612
Lysosome docking to WIPI1 rings and ER-connected phagophores occurs during DNAJB12- and GABARAP-dependent selective autophagy of misfolded P23H-rhodopsin [ Mol Biol Cell, 2022, 33(9):ar84]	PubMed: 35704470
Protective Mechanism of Berberine on Human Retinal Pigment Epithelial Cells against Apoptosis Induced by Hydrogen Peroxide via the Stimulation of Autophagy [ Oxid Med Cell Longev, 2021, 2021:7654143]	PubMed: 34422209
GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis [ Sci Adv, 2021, 7(40):eabj2485]	PubMed: 34597140
Sorting nexin 5 mediates virus-induced autophagy and immunity [ Nature, 2020, 10.1038/s41586-020-03056-z]	PubMed: 33328639

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SHIPPING AND STORAGE
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