VPS34-IN-1

VPS34-IN-1 : Inhibitor of PIK3C3

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe VPS34-IN-1 is in the process of SERP review.

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Information

PIK3C3

Inhibitor

from 100 nM up to 1 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q8NEB9

Target Class: Kinase

Target SubClass: PI3/PI4-kinase family

Potency: IC50

Potency Value: 28 nM

Potency Assay: Phosphorylation of PtdIns in a 32P‐radioactive kinase assay by Selectscreen biochemical kinase profiling

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Phosphatidylinositol 3-kinase catalytic subunit ty ...

DOI Reference: 10.1042/BJ20140889

Uniprot ID: Q8NEB9

Target Class: Kinase

Target SubClass: PI3/PI4-kinase family

Potency: IC50

Potency Value: 25 nM

Potency Assay: Recombinant human Vps34–Vps15 complex was assayed by measuring phosphorylation of PtdIns in a 32P-radioactive kinase assay

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Phosphatidylinositol 3-kinase catalytic subunit ty ...

DOI Reference: 10.1042/BJ20140889

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Protein kinase profiling of the VPS34-IN1 at a single concentration of 1 μM carried out against the Dundee panel of 140 protein kinases at the International Centre for Protein Kinase Profiling. Protein kinase profiling of the VPS34‐IN1 at a single concentration of 1μM carried out against the ProQinase panel of 300 protein kinases. VPS34-IN1 was remarkably selective and, at a concentration of 1 μM, did not significantly inhibit the activity of the protein kinases assessed. VPS34-IN1 was assessed against three different lipid kinase profiling panels namely the Dundee panel (19 lipid kinases, includes class I PI3Ks), the AstraZeneca panel (8 lipid kinases, includes class I) and ProQuinase panel (13 lipid kinases, includes class I and class II PI3Ks). This revealed that VPS34-IN1 did not significantly inhibit any of the lipid kinases tested including class I (p110α, p110β p110γ and p110δ) and all three members of the class II PI3Ks (PI3KC2α, PI3KC2β and PI3KC2γ) enzymes.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Direct target engagement in cells has not been demonstrated.

(last updated: 30 Oct 2024 )

SERP Ratings

In Cell Rating

SERP Comments:

VPS34-IN-1 is a moderately potent (25nM biochemical, 0.1-1uM cellular) and very selective kinase inhibitor. It shows 50-fold or more selectivity against other lipid kinases, and a very clean profile in broad kinome panel profiling. Although there is no direct measurement of target engagement, the phosphorylation level of the kinase substrate is shown to be modulated by the inhibitor in cells. A negative control is not provided - we recommend that a second orthogonal probe VPS34 inhibitor e.g. SAR405 is used to confirm findings with this compound.

(last updated: 20 Feb 2025 )