T-10418

T-10418 : Agonist of GPR132

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 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

GPR132

Agonist

up to 1 uM
Reviewer recommended concentration: up to 10 µM based on EC50 and good selectivity profile

In Vitro Validations

No in Vitro Validations

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): T-10418 was tested for GPCR selectivity in the PRESTO-Tango assay that measures association of a receptor with β-arrestin. The assay panel is covering more than 300 nonolfactory GPCRs. Apart from the expected G2A activation, T-10418 showed activity only on one other receptor, GPR1 (human protein sequence), which suggests excellent GPCR selectivity. T-10418 was also profiled in the SafetyScreen44 Panel from Eurofins showing inhibition of specific binding by <25% across the entire set.

Potency assay, off target (cells): Potential off-targets were tested using HEK293 cells stably express CMKLR1-eYFP or GPR1-eYFP treated with 30 uM T-10418. T-10418 shows only partial agonism on GPR1 in BRET assay.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 30 Jul 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

While the agonistic potency, in vivo PK, and relevant data are not sufficient for routine use of this compound in investigating GPR132 biology/physiology, this compound could be considered the best option available as of today. I hope that the open scientific community will utilize this compound to gather more data and understand its scientific usefulness and limitations. Further compound optimization would be a future goal.

(last updated: 31 Jul 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Due to its relatively weak potency this is not an ideal probe to study the biology of GPR132 in vitro, however there is limited choice for this target so it can be used with caution. The mouse PK data in the paper shows a Cmax of around 2 uM (approx. 2.5 x the EC50) after dosing at 10 mg/kg sc. It is difficult to say if this is adequate target coverage to show effects in vivo.

(last updated: 15 Aug 2024 )