Transcription Factor Inhibition: Lessons Learned and Emerging Targets

Abstract

Transcription factors have roles at focal points in signaling pathways, controlling many normal cellular processes, such as cell growth and proliferation, metabolism, apoptosis, immune responses, and differentiation. Their activity is frequently deregulated in disease and targeting this class of proteins is a major focus of interest. However, the structural disorder and lack of binding pockets have made design of small molecules for transcription factors challenging. Here, we review some of the most recent developments for small molecule inhibitors of transcription factors emphasized in James Darnell's vision 17 years ago. We also discuss the progress so far on transcription factors recently nominated by genome-scale loss-of-function screens from the cancer dependency map project.

Keywords: Myb; Myc; NF-κB; STAT; chemical probe; transcription factor.