SEW-2871

SEW-2871 : Full agonist of S1PR1

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe SEW-2871 is in the process of SERP review.

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Information

S1PR1

Full agonist

500 nM

Probe Availability:

In Vitro Validations

Uniprot ID: P21453

Target Class: GPCR

Target SubClass: Sphingosine receptor

Potency: EC50

Potency Value: 13 ± 8.58 nm

Potency Assay: GTPγS binding assays measured in CHO cell membranes expressing stably transfected hS1P1 receptor

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

Target aliases:

Sphingosine 1-phosphate receptor 1, EDG1, CHEDG1, ...

DOI Reference: 10.1074/jbc.M311743200

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): Selectivity within target family: SEW2871 was inactive at 10,000 nM on hS1P2, hS1P3, hS1P4, and hS1P5.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Historically, SEW2871 was a useful chemical probe as it enabled determination of what S1P receptor isoform drives disruption of lymphocyte trafficking (S1P1) vs. the receptor isoform driving bradycardia in rodents (S1P3). However, SEW2871 has limited solubility, is less potent than follow on S1P1-selective receptor agonists and is reported to be toxic in a sepsis model. Many S1P receptor agonists have been reported subsequent to the discovery of SEW2871. Ponesimod, for example, is superior to SEW2871 for in vitro and in vivo studies.

(last updated: 21 Nov 2022 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

SEW-2871 is a potent agonist for S1PR1. Despite showing reasonable selectivity against other S1PR1 subtypes, no further selectivity or off-target data is known (e.g. affinity-based protein profiling target engagement data). Other probes such as ponesimod offer a more potent, soluble and selective (S1PR1) alternative to SEW-2871.

(last updated: 5 Dec 2022 )