IRAK3-PROTAC 23

IRAK3-PROTAC 23 : Degrader (PROTAC) of IRAK3

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 ratings)

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Information

IRAK3

Degrader (PROTAC)

100 nM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q9Y616

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 4.9 nM

Potency Assay: Enzymatic binding assay

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

Target aliases:

Interleukin-1 receptor-associated kinase 3, IRAK3, ...

DOI Reference: 10.1021/acs.jmedchem.0c01125

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Selectivity within family: Selective against IRAK4 1400 nM and IRAK1 2300 nM. Kinome selectivity of PROTAC 23: tested at 0.1 μM in a panel of 400 kinases. Only four other kinases were identified with >50% activity: CDK11 (82%, IC50 = 16 nM), CDK8 (69%, IC50 = 36 nM), TRKC (60%, IC50 = 100 nM), and GSG2 (57%, IC50 = 1610 nM)

Potency assay, off target (cells): Selective degradation was confirmed using global proteomic profiling in THP1 cells where only IRAK3 and DHCR24 were significantly decreased upon PROTAC treatment with fold changes of −1.8 and −1.5, respectively (p < 0.05), while changes for IRAK1 and IRAK4 were negligible. Upon closer examination, binding to DHCR24 was found to be incomplete (<40% binding at the highest concentration, 30 μM.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

This compound is recommended as an in vitro tool. It has not been validated for in vivo use.

(last updated: 13 Oct 2023 )

SERP Ratings

In Cell Rating

SERP Comments:

IRAK3-PROTAC 23 is a great chemical probe for in cellulo experiments. This PROTAC exhibits very potent degradation of IRAK3 in THP1 cell line. The mechanism of acion has been well investigated. The inhibitory effect for kinases has been evaluated using a panel of 400 kinases. The selectivity of degradation has been throughly assessed using MS-proteomics, showing selective IRAK3 degradation at 0.1 uM concentration in THP1 cell line. The user should keep in mind that the potency as well as selectivity may vary in different cell lines.

(last updated: 24 Dec 2023 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

IRAK3-PROTAC 23 shows potent degredation of IRAK3 in the THP1 cell line and primary macrophages. Global proteomics show selective IRAK3 degradation compared at 100 nM concentration in THP1 cells. One cell line was used. Care should be taken that the concentration of 100 nM may be appropriate only for THP1 cells.

(last updated: 31 Oct 2024 )