A-446

A-446 : Inhibitor of GLS

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 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.

Probe A-446 is in the process of SERP review.

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Information

Inhibitor

10 nM

Additional Data

SGC image SGC Chemical Probe Collection

In Vitro Validations

Uniprot ID: O94925

Target Class: Enzyme

Target SubClass: Glutaminase

Potency: IC50

Potency Value: 31 nM

Potency Assay: GAC (GLS) Enzyme activity assay

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

Target aliases:

Glutaminase kidney isoform, mitochondrial, KIAA083 ...

Other Reference: not yet available

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Selectivity within target family - GLS2 Enzyme activity assay: IC50 > 30 µM (>1000-fold selectivity). Selectivity outside target family - Probe selectivity observed in Proteome Integral Stability Assay. Closest off-targets in Cerep binding assay at 10 μM (percent inhibition of control specific binding): ADORA3 ( agonist radioligand) 76.6%, CHRM1 (antagonist radioligand) 92.6%, CHRM2 (antagonist radioligand) 71.5%

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

According to the in-vitro inhibitory potency, selectivity, and the clean CEREP panel A-446 has high potential to be a recommendable chemical probe. However, there are curently no publications on the use of A-446 in biological model systems.

(last updated: 22 May 2022 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

A-446 is a useful chemical probe for GLS2. It appears to be the best available probe for this target. At this time, there are no peer-reviewed publications describing this probe so a more robust assessment of the probe quality is difficult. The probe has good reported local selectivity and acceptable broad selectivity profile. Having concentration-response data for the observed off targets (such as CHRM1) would be useful. The accompanying negative control adds value to practical use of this chemical probe.

(last updated: 14 Jun 2022 )