PF470

PF470 : Negative Allosteric Modulator of GRM5

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe PF470 is in the process of SERP review.

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Information

GRM5

Negative Allosteric

up to 1 uM

Probe Availability:

In Vitro Validations

Uniprot ID: P41594

Target Class: GPCR

Target SubClass: Metabatropic Glutamate Receptor

Potency: Ki

Potency Value: 0.9 nM

Potency Assay: Human mGluR5 Radioligand Binding Assay

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

Structure-activity relationship: yes

Target aliases:

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

DOI Reference: 10.1021/jm401622k

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Selective vs mGLU1 (IC50 = 30.5 uM), PF470 showed no apparent functional agonism (orthosteric or allosteric) or antagonism activities at any other mGluR up to 50 μM. Outside Target Family: Broader selectivity screening with PF470 revealed no significant activities in kinase panels (<50% inhibition at 10 uM), a proprietary phosphodiesterase (PDE) panel (IC50 > 10 μM), and a broad spectrum BioPrint panel in which the adenosine A2A receptor had the highest affinity (Ki = 6.1 μM).

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

PF470 is a well-characterized negative allosteric modulator for mGluR5. Together with HTL14242 (also rated in this portal) both can be used as orthogonal chemical probes to study mGluR5 pharmacology. PF470 is potent (IC50 = 0.9 nM) and selective versus other members of the mGluR family as well as other broader selectivity panels. On-target bindind is supported by a homology model. The good PK properties of PF470 allows usage in rats and monkeys.

(last updated: 7 Apr 2025 )