PIK-III


Catalog No. size PriceQuantity
M6477-2 2mg solid $106
M6477-10 10mg solid $436

Description

Cas:1383716-40-2

Product Information:

PIK-III, also known as VPS34-IN2, is a VPS34 inhibitor which blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. PIK-III binds a unique hydrophobic pocket not present in related kinases such as PI(3)Kα. PIK-III acutely inhibits autophagy and de novo lipidation of LC3, and leads to the stabilization of autophagy substrates.

 

Chemical Formula: C17H17N7

 

Exact Mass: 319.1545

 

Molecular Weight: 319.372

 

Elemental Analysis: C, 63.93; H, 5.37; N, 30.70

 

Synonym:

 

PIK-III

VPS34-IN2

VPS34-IN 2

VPS34-IN-2

 

Chemical Name:

4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)-[4,5'-bipyrimidine]-2,2'-diamine

 

InChi Key:

XXSDLQLNIVFIJI-UHFFFAOYSA-N

 

InChi Code: 

InChI=1S/C17H17N7/c18-16-21-10-13(15(23-16)9-11-1-2-11)14-5-8-20-17(24-14)22-12-3-6-19-7-4-12/h3-8,10-11H,1-2,9H2,(H2,18,21,23)(H,19,20,22,24)

 

Smiles Code:

NC1=NC=C(C2=NC(NC3=CC=NC=C3)=NC=C2)C(CC4CC4)=N1

 

 

Technical Data:

 

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

 

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 leads to an increase in the levels of LC3-I in H4 and PSN1 cells.

 

In Vivo:

The DFX-induced NCOA4-dependent turnover of FTH1 and FTL is blocked with PIK-III suggesting an autophagy-dependent process.

 

 

References

 

  1. Dowdle WE, Nyfeler B, Nagel J, Elling RA, Liu S, Triantafellow E, Menon S, Wang Z, Honda A, Pardee G, Cantwell J, Luu C, Cornella-Taracido I, Harrington E, Fekkes P, Lei H, Fang Q, Digan ME, Burdick D, Powers AF, Helliwell SB, D'Aquin S, Bastien J, Wang H, Wiederschain D, Kuerth J, Bergman P, Schwalb D, Thomas J, Ugwonali S, Harbinski F, Tallarico J, Wilson CJ, Myer VE, Porter JA, Bussiere DE, Finan PM, Labow MA, Mao X, Hamann LG, Manning BD, Valdez RA, Nicholson T, Schirle M, Knapp MS, Keaney EP, Murphy LO. 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. doi: 10.1038/ncb3053. Epub 2014 Oct 19. PubMed PMID: 25327288.

 

Products are for research use only. Not for human use.

 

 

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