Vps34-PIK-III

Modify Date: 2024-01-04 15:39:41

Vps34-PIK-III Structure
Vps34-PIK-III structure
Common Name Vps34-PIK-III
CAS Number 1383716-40-2 Molecular Weight 319.36400
Density N/A Boiling Point N/A
Molecular Formula C17H17N7 Melting Point N/A
MSDS N/A Flash Point N/A

 Use of Vps34-PIK-III


Vps34-PIK-III is a potent and selective inhibitor of VPS34 with an IC50 of 18 nM.

 Names

Name pik-iii
Synonym More Synonyms

 Vps34-PIK-III Biological Activity

Description Vps34-PIK-III is a potent and selective inhibitor of VPS34 with an IC50 of 18 nM.
Related Catalog
Target

Vps34:18 nM (IC50)

PI(3)Kδ:1.2 μM (IC50)

PI(3)Kγ:3.04 μM (IC50)

PI(3)Kα:3.96 μM (IC50)

Autophagy

In Vitro PIK-III is a selective inhibitor of VPS34 that binds a unique hydrophobic pocket not present in related kinases such as PI3Kα. PIK-III is at least 100-fold-selective for VPS34 over related lipid kinases such as PI3K and the protein kinase mTOR. PIK-III acutely inhibits autophagy and de novo lipidation of LC3, and leads to the stabilization of autophagy substrates. In H4 cells expressing the mCherry-GFP-LC3 reporter PIK-III inhibits the formation of mCherry-positive autolysosomes and increases the cytosolic signal of LC3 under basal conditions and when autophagy is induced with the mTOR inhibitor AZD8055. PIK-III prevents the turnover of GFP-tagged p62 under basal conditions and when autophagy is activated. PIK-III treatment leadsto an increase in the levels of LC3-I in H4 and PSN1 cells[2].
In Vivo The DFX-induced NCOA4-dependent turnover of FTH1 and FTL is blocked with PIK-III suggesting an autophagy-dependent process[2].
References

[1]. Honda A, et al. Potent, Selective, and Orally Bioavailable Inhibitors of VPS34 Provide Chemical Tools to Modulate Autophagy in Vivo. ACS Med Chem Lett. 2015 Nov 13;7(1):72-6.

[2]. Dowdle WE, et al. Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat Cell Biol. 2014 Nov;16(11):1069-79.

 Chemical & Physical Properties

Molecular Formula C17H17N7
Molecular Weight 319.36400
Exact Mass 319.15500
PSA 102.50000
LogP 3.26110
Storage condition -20℃

 Synonyms

4'-cyclopropylmethyl-N2-pyridin-4-yl-[4,5']bipyrimidinyl-2,2'-diamine
4'-cyclopropylmethyl-N2-pyridin-4-yl-[4,5'] bipyrimidinyl-2,2'-diamine
Vps34-PIK-III
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