Targeting TAK1

evolution of inhibitors, challenges, and future directions

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

Abstract

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.

Keywords

transforming growth factor-β-activated kinase 1;inhibitors;inflammation;tumor necrosis factor;signaling pathways;structure-activity relationship;

Data

Language:	English
Year of publishing:	2025
Typology:	1.02 - Review Article
Organization:	UL FFA - Faculty of Pharmacy
UDC:	615.4:54
COBISS:	224969475
ISSN:	1879-016X
Views:	23
Downloads:	9
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	transformacijski rastni faktor-β-aktivirana kinaza 1;inhibitorji;vnetje;faktor tumorske nekroze;signalne poti;razmerje struktura-aktivnost;Farmacevtska kemija;
Type (COBISS):	Article
Pages:	<v tisku>
Volume:	ǂVol. ǂ
Issue:	[article no.] 108810
Chronology:	2025
DOI:	10.1016/j.pharmthera.2025.108810
ID:	25877355