TAK-279

TAK-279 : Inhibitor of TYK2

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe TAK-279 is in the process of SERP review.

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Information

TYK2

Inhibitor

up to 10 nM
Reviewer recommended concentration: up to 100 nM in cells and 1 µM in whole blood

Probe Availability:

In Vitro Validations

Uniprot ID: P29597

Target Class: Kinase

Target SubClass: Tyrosine Kinase

Potency: Kd

Potency Value: 0.0038 nM

Potency Assay: human TYK2 JH2 inhibition assay

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

Target aliases:

Non-receptor tyrosine-protein kinase TYK2, TYK2, T ...

DOI Reference: 10.1021/acs.jmedchem.3c00600

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): Compound 30 exhibits excellent overall kinome selectivity, with only 1 kinase inhibited at >50% in a panel of 631 kinases ([compound 30] = 1 μM, [ATP] = 10 μM).

Potency assay, off target (cells): Compound 30 exhibited a higher level of functional selectivity in cellular and whole blood assays that evaluate signaling through JAK1, JAK2, or JAK3. 30 was selective in cell assays dependent on JAK1 signaling: in IL2-stimulated CD3+ T-cells, 30 did not inhibit phosphorylation of STAT5 (IC50 > 50,000 nM). In IL6-stimulated CD3+ T-cells 30 exhibited no inhibition (IC50 > 30,000 nM) of phosphorylation of STAT3. In IL22-stimulated HT-29 cells, 30 also exhibited no inhibition (IC50 > 30,000 nM) of phosphorylation of STAT3.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The compound is an allosteric TYK2 inhibitor targeting the regulatory JH2 domain. It is highly selective against other JAK isoforms, within teh kinome, as well as in a broader off-target/safety panel. Selectivity is slightly superior to the approved TYK2 inhibitor deucravacitinib. The compounds may be used up to 100 nM in cells and 1 µM in whole blood. The compound is currently in phase II clinical trials and suitable for in vivo use in rat, mouse and presumably various other model organisms. Use of a spray-dry dispersions (SDD) for oral dosing improves bioavailability/exposure. Unfortunately the compounds does not come with a suitable negative control.

(last updated: 3 Nov 2024 )