Targeting TAK1 : evolution of inhibitors, challenges, and future directions

Strašek Benedik, Nika (author), Proj, Matic (author), Steinebach, Christian (author), Sova, Matej (author), Sosič, Izidor (author)

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.

• Language: English
• Keywords: transforming growth factor-β-activated kinase 1, inhibitors, inflammation, tumor necrosis factor, signaling pathways, structure-activity relationship
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 20 str.
• Numbering: Vol. 267, art. 108810
• PID: 20.500.12556/RUL-167118
• UDC: 615.4:54
• ISSN on article: 1879-016X
• DOI: 10.1016/j.pharmthera.2025.108810
• COBISS.SI-ID: 224969475
• Publication date in RUL: 10.02.2025

Record is a part of a journal

• Title: Pharmacology & therapeutics
• Shortened title: Pharmacol. ther.
• Publisher: Elsevier
• ISSN: 1879-016X
• COBISS.SI-ID: 72613891

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: transformacijski rastni faktor-β-aktivirana kinaza 1, inhibitorji, vnetje, faktor tumorske nekroze, signalne poti, razmerje struktura-aktivnost, farmacevtska kemija