BI01383298

BI01383298 : an irreversible inhibitor of SLC13A5

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe BI01383298 is in the process of SERP review.

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Information

SLC13A5

irreversible

up to 1 uM

Additional Data

SGC Chemical Probe Collection

Probe Availability:

MCULE

In Vitro Validations

Uniprot ID: Q86YT5

Target Class: Transporter

Target SubClass: Solute transporter

Potency: ΔTm

Potency Value: > 10 K @ 10 uM

Potency Assay: Thermo Stabilisation Assay

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

Target aliases:

Na(+)/citrate cotransporter, NACT, SLC13A5, S13A5_ ...

DOI Reference: 10.1042/BCJ20200592

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): BI01383298 is more than 1000-fold selective (table 1) over the closest family members: human SLC13A2 / SLC13A3 that share physiological substrates citrate and succinate.

Potency assay, off target (cells): Citrate uptake inhibition was measured for all citrate transporters and glycine uptake measured to GLYT2. Potency was assessed for the probe candidate and the negative control on uptake of 14C-citrate into cells over-expressing SLC13A5, SLC13A2, SLC13A3, mouse SLC13A5 and in HEPG2 cells.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Due to the non-reversible mechanism of action of BI01383298, a pre-incubation of 30 minutes is required to achieve maximal inhibition of cellular uptake of citrate. Of note, using kinetic analysis of citrate uptake inhibition, the authors show that BI01383298 has a non-competitive mechanism of action. However, they also propose and modeled binding of the compound in the citrate binding site, which is in contradiction. Also of note, while BI01383298 was shown to inhibit citrate uptake in an irreversible manner, no data supporting a covalent interaction were provided and the irreversibility can be due to a variety of factors, which should be further studied to increase our understanding of the mechanism of action of BI01383298 and our confidence as a tool compound to study NaCT biology

(last updated: 5 Feb 2023 )

SERP Ratings

In Cell Rating

SERP Comments:

Available data for this probe consists exclusively of cellular inhibition experiments. No direct binding has been demonstrated via biochemical or biophysical approaches.

(last updated: 9 Feb 2023 )