Targeting TAK1: Evolution of inhibitors, challenges, and future directions.

The increasing incidence of inflammatory and malignant diseases signifies the need to develop first-in-class drugs with novel mechanisms of action. In this respect, the transforming growth factor (TGF)-β-activated kinase 1 (TAK1), an essential part of several signaling pathways, is considered relevant and promising. This manuscript provides a brief overview of the signal transduction orchestrated by TAK1 within these pathways, followed by an in-depth and thorough analysis of the chemical matter demonstrated to inhibit this kinase. Special attention is given to the selectivity profiling of inhibitors, as well as to the outcomes of their biological characterization. Because published TAK1 inhibitors differ significantly in their kinome selectivity, active-site binding, and biological activity, we hope that this review will allow a judicial estimation of their quality and usefulness for TAK1-addressing assays. Our thoughts on the perspectives and possible developments of the field are also provided to assist scientists who are involved in the design and development of TAK1-targeting modulators.

• Publication year

  2025

• Venue

  Pharmacology and Therapeutics

• Publication date

  2025-02-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.pharmthera.2025.108810PMID 39909209
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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