SAR405

SAR405 : Inhibitor of PIK3C3

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

PIK3C3

Inhibitor

1 uM

Probe Availability:

In Vitro Validations

Uniprot ID: Q8NEB9

Target Class: Kinase

Target SubClass: PI3/PI4 Kinase

Potency: IC50

Potency Value: 1 nM

Potency Assay: Phosphorylation of a PtdIns substrate by human recombinant Vps34 enzyme

PDB ID for probe-target interaction (3D structure): 4OYS

Target aliases:

Phosphatidylinositol 3-kinase catalytic subunit ty ...

DOI Reference: 10.1038/nchembio.1681

Uniprot ID: Q8NEB9

Target Class: Kinase

Target SubClass: PI3/PI4 Kinase

Potency: Kd

Potency Value: 1.5 nM

Potency Assay: Surface Plasmon Resonance (SPR) technology using immobilized human Vps34 protein; koff, of 3.03 ± 0.55 10−3 s−1, corresponding to a residence half-life, t1/2, of 3.8 min

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

Target aliases:

Phosphatidylinositol 3-kinase catalytic subunit ty ...

DOI Reference: 10.1038/nchembio.1681

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

The selectivity of SAR405 was determined in a panel of biochemical assays. SAR405 was found to not be active up to 10 μM on class I and class II PI3Ks as well as on mTOR (PI3K class I (α β δ γ), PI3K class II (α β γ) and mTOR with IC50 > 10000 nM). SAR405 profiling was extended to a panel of more than 200 endogenous kinases using KiNativ chemoproteomics at ActivX Biosciences and Jurkat cells. Moderate binding was found only with PI3K class I α, β and δ isoforms at 1 μM (39%, 68% and 63% inhibition, respectively). No binding of SAR405 was measured on any protein kinases in the panel, with the exception of SMG1 (52% inhibition at 1 μM.

Potency assay, off target (cells): Meso Scale electrochemiluminescence technology on phosphorylated Akt

Probe Selectivity in Cell:

Selective over class I PI3Ks with IC50s of ∼7 μM and 6 μM for SAR405 in U87MG and PC3 cell lines, respectively.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Excellent Vsp34 PI3K class III isoform probe for use in the study of autophagy

(last updated: 12 Aug 2022 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

The probe has a good in vitro potency, but in cell potency is low. It can be used as a lead compound for further investigation. Also, the cytotoxicity assay was not evaluated.

(last updated: 23 May 2024 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

Very potent compound targeting Vps34 with high selectivy in the lipid kinase family extended to a panel of 200 endogenous kinases.

(last updated: 23 Sept 2024 )