BAY 2413555

BAY 2413555 : Positive allosteric modulator of CHRM2

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 BAY 2413555 is in the process of SERP review.

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Information

CHRM2

Positive allosteric

300 nM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: P08172

Target Class: GPCR

Target SubClass: Muscarinic receptor

Potency: Kd

Potency Value: 17 nM

Potency Assay: Radioligand binding assay at saturating concentration of acetylcholine (100 μM)

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

Target aliases:

Muscarinic acetylcholine receptor M2, CHRM2, ACM2_ ...

DOI Reference: 10.1021/acs.jmedchem.4c01590

Uniprot ID: P08172

Target Class: GPCR

Target SubClass: Muscarinic receptor

Potency: Ki

Potency Value: 7.6 ± 4 nM

Potency Assay: Competitive radioligand binding assay

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

Target aliases:

Muscarinic acetylcholine receptor M2, CHRM2, ACM2_ ...

DOI Reference: 10.1021/acs.jmedchem.4c01590

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): Within target family: Potential allosteric agonism of compound BAY 2413555 both on the human M2 receptor and its human paralogues (M1, M3, M4, and M5 receptors) was assessed using orthogonal functional Ca2+ mobilization assays in agonistic (compound only) and cooperativity mode. BAY 2413555 is a highly selective PAM for the M2 receptor and exerts no significant allosteric effects on other human muscarinic acetylcholine receptors. Outside target family: When tested at 10 μM in a broad panel of safety relevant off-target proteins covering GPCRs, enzymes, nuclear hormone receptors, transporters, and ion channels, BAY 2413555 showed binding to one off-target protein only, the rat GABAA chloride channel (TBOB binding site), with a Ki of 7.1 μM.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

BAY-2413555 is a high quality positive allosteric modulator of CHRM2 that can be used in vitro and in vivo with confidence. Based on the rat telemetry study in the J Med Chem paper, I suggest 3-10 mg/kg as a suitable dose in rat studies, and 1-3 mg/kg in cynomolgous monkey.

(last updated: 13 Dec 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Toxicity in monkeys (increased vascular inflammation) was observed. [PMID: 39738130; PMCID: PMC11685975; DOI: 10.1038/s41598-024-77111-4]

(last updated: 26 Jan 2025 )