Characterization of the Binding of Small Molecules to Intrinsically Disordered Proteins.

Intrinsically disordered proteins (IDPs) comprise a large fraction of eukaryotic proteomes. IDPs are prevalent in cellular regulation, signaling networks, and disease pathways. The abundance and activity of IDPs is tightly controlled at multiple levels, and their dysregulation is associated with disease.

Single enantiomer of YK-4-279 demonstrates specificity in targeting the oncogene EWS-FLI1.

Oncogenic fusion proteins, such as EWS-FLI1, are excellent therapeutic targets as they are only located within the tumor. However, there are currently no agents targeted toward transcription factors, which are often considered to be 'undruggable.' A considerable body of evidence is accruing that refutes this claim based upon the intrinsic disorder of transcription factors.