UCSF7447

Inverse Agonist of MTNR1A

Structure

Information

Protein target names: MTNR1A

Mechanism of action: Inverse Agonist

Recommended in-cell concentration:
Up to 1 uM

In Vitro Validations

Uniprot ID: P48039
Target Class: GPCR
Target SubClass: Melatonin Receptor
Potency: Ki
Potency Value: 7.5 nM
Potency Assay: Radioligand Binding
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Melatonin receptor type 1A, MTNR1A, MTR1A_HUMAN, M ...

DOI Reference: 10.1038/s41586-020-2027-0

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

ZINC555417447 is a brain penetrant, inverse agonist (partial 62% Emax) of the Melatonin MT1 receptor, with good selectivity over the related MT2 receptor (53-fold selective in human and 158-fold in mouse). Although it has a relatively short half-life in vivo (it is comparable to the half-life of melatonin), as an inverse agonist it demonstrates an opposing effect to the natural agonist melatonin in a mouse model of ‘jet-lag’ at low doses (0.03 mg/kg s.c.). Importantly, the compound’s effects in vivo are eliminated in a mouse MT1-knockout and enhanced in an MT2-knockout. Together, the data supports its use in both cells and in vivo mouse models to investigate the role of MT1. The structurally related MT2 agonist ZINC128734226 would a useful probe to use alongside ZINC555417447 in any cell or in vivo experiments. 

(last updated: 19 May 2020 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Thorough characterization has been performed by trustworthy scientists; an inactive analog (ZINC37781618) and an analogous, active probe for the related MT2 receptor (ZINC128734226) were characterized in parallel and provide a set of valuable tools to interrogate melatonin receptor pharmacology.

(last updated: 30 Jul 2021 )