UCSF4226

Agonist of MTNR1B

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

MTNR1B

Agonist

up to 1 uM

DOI - 10.1038/s41586-020-2027-0

In Vitro Validations

Uniprot ID: P49286

Target Class: GPCR

Target SubClass: Melatonin Receptor

Potency: Ki

Potency Value: 63 nM

Potency Assay: Radioligand binding

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

Target aliases:

Melatonin receptor type 1B, MTNR1B, MTR1B_HUMAN, M ...

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

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Screened for radioligand binding modulation of CNS GPCRs and toxic pharmacological off-targets at 10uM, no activity was observed.

Probe Selectivity in Cell:

Counter-screened against MTNR1A and was >54-fold selective for MTNR1B. Also screened against a panel of 318 GPCRs at 10uM. Secondary concentration-response assays of preliminary hits demonstrated no replicable off-target action.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Outstanding characterisation of this probe. I recommend its use in animals and in cells to selectively modulate MT activity.

(last updated: 2 Jun 2020 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This is clearly a good probe candidate but from a single publication so far. The two melatonic receptor human paralogues are well studied pharmacologically so additional compounds and controls are also available for comparative testing.

(last updated: 7 Jun 2020 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

UCSF4226 is a high affinity brain-penetrant inverse agonist of melatonin receptor MTNR1B (MT2). Sufficient selectivity against GPCR target family and common off-targets has been demonstrated. Cellular activity was demonstrated in HEK293 and CHO cell lines. The selectivity for MT2 over MT1 was demonstrated in vitro for the human receptor only, the selectivity was lost for the mouse receptor and was not assessed in other species. In vivo pharmacology evaluation has not been performed.

(last updated: 24 Sept 2020 )