Disruption of protein–protein or protein–DNA interactions involved in transcriptional machinery using small molecules poses a real challenge owing to several factors, including: the large interfacial areas involved, the lack of obvious binding sites, and the large free energy of association between the interfaces.
However, in recent years there has been considerable success in the dimeric transcription factor disruption using small molecules. Steven Fletcher and co-workers at University of Maryland School of Pharmacy, provide a review of the progress made in this area since 2008.
This review covers:
- Inhibitors of STAT3
- Inhibitors of c-Myc
- Inhibitors of AP-1
- Inhibitors of HIF-1
Small-molecule inhibitors of dimeric transcription factors: Antagonism of protein–protein and protein–DNA interactions
Jeremy L. Yap, Jay Chauhan, Kwan-Young Jung, Lijia Chen, Edward V. Prochownik and Steven Fletcher
Med. Chem. Commun., 2012,
DOI: 10.1039/C2MD00289B, Review
