|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Henley, MJ, Koehler, AN|
|Journal||Nat Rev Drug Discov|
|Date Published||2021 May 18|
Transcription factors (TFs) represent key biological players in diseases including cancer, autoimmunity, diabetes and cardiovascular disease. However, outside nuclear receptors, TFs have traditionally been considered 'undruggable' by small-molecule ligands due to significant structural disorder and lack of defined small-molecule binding pockets. Renewed interest in the field has been ignited by significant progress in chemical biology approaches to ligand discovery and optimization, especially the advent of targeted protein degradation approaches, along with increasing appreciation of the critical role a limited number of collaborators play in the regulation of key TF effector genes. Here, we review current understanding of TF-mediated gene regulation, discuss successful targeting strategies and highlight ongoing challenges and emerging approaches to address them.
|Alternate Journal||Nat Rev Drug Discov|