HTL14242

Negative Allosteric Modulator of GRM5

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

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Probe HTL14242 is in the process of SERP review.

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Information

GRM5

Negative Allosteric Modulator

Probe Availability:

In Vitro Validations

Uniprot ID: P41594

Target Class: GPCR

Target SubClass: Metabatropic Glutamate Receptor

Potency: pKi

Potency Value: 9.3

Potency Assay: [3H]-M-MPEP Binding Assay

PDB ID for probe-target interaction (3D structure): 5CGD

Structure-activity relationship: yes

Target aliases:

Metabotropic glutamate receptor 5, MGLUR5, GPRC1E, ...

DOI Reference: 10.1021/acs.jmedchem.5b00892

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Cell:

Cross-screened in an external panel (Eurofins) of 30 GPCR, kinase, ion-channel, and transporter targets, where the compound displayed at least 1000-fold selectivity against the panel members. HTL14242 was profiled in agonist, positive allosteric modulator (PAM), and antagonist/NAM modes against all eight mGlu receptors in an external screen (Euroscreen) displaying an excellent selectivity profile, with no appreciable receptor activation in agonist or PAM modes against any of the mGlu receptors. No appreciable inhibition was observed for mGlu1,2,4,6–8 in antagonist/NAM mode, with activity at the mGlu5 receptor (97% inhibition at 10 μM). A small degree of mGlu3 inhibition was noted (47% inhibition at 10 μM).

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

It is important to note that a metal-binding motif is present in the molecule so the presence of metal in in vitro assays for example could impact results with this compound.

(last updated: 6 Oct 2021 )