Emavusertib

Emavusertib : Inhibitor of IRAK4

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe Emavusertib is in the process of SERP review.

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Information

IRAK4

Inhibitor

up to 5 uM
Reviewer recommended concentration: up to 1 µM to limit off-target effect (CLK-family)

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q9NWZ3

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 31.7 nM

Potency Assay: TR-FRET assay using recombinant IRAK4 kinase

PDB ID for probe-target interaction (3D structure): 7C2V

Target aliases:

Interleukin-1 receptor-associated kinase 4, IRAK4, ...

DOI Reference: 10.1021/acsmedchemlett.0c00255

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): Evaluated in a broad kinome panel (Eurofins, 329 kinases) at 1 µM and 10 µM. Apart from IRAK4, Emavusertib was also observed to be exhibiting significant activity (≥50% inhibition at 1 μM) in a handful of other kinases such as CLK1, CLK2, CLK4, FLT3, DYRK1A, DYRK1B, TrkA, TrkB, Haspin, and NEK11. Also tested in small panel of kinases at 100 nM and 1 µM, showing some inhibition of FLT3.

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SERP ratings and comments

SERP+ Ratings

In Cell Rating

In Model Organisms

SERP+ Comments:

The probe is generally well characterized and optimized for in vivo use. At 1 µM four other kinases (FLT3, CLK1, CLK2 and CLK4) are inhibited >90% (target inhibiton at this conectration = 82%). The compound is profiled extensively in model organisms (mouse, rat and dog) and has very good oral bioavailability. The in vivo activity was confirmed in xenograft models. A control compound is missing. At the moment (Mar 2023), it is one of the best tool compounds but care has to be taken regarding possible off-targets. The use of orthogonal probes is highly recommended.

(last updated: 22 Mar 2023 )