Protein Degradation

Machine learning modeling of protein-intrinsic features predicts tractability of targeted protein degradation

Targeted protein degradation (TPD) has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell’s endogenous protein degradation machinery. However, the susceptibility of proteins for targeting by …

BTBBCL6 dimers as building blocks for reversible drug-induced protein oligomerization

Here, we characterize the BTB domain of the transcription factor BCL6 (BTBBCL6) as a small-molecule-controlled, reversible oligomerization switch, which oligomerizes upon BI-3802 treatment and de-oligomerizes upon addition of BI-3812. We show that …

Small molecule-induced polymerization triggers degradation of BCL6

Effective and sustained inhibition of non-enzymatic oncogenic driver proteins is a major pharmacological challenge. The clinical success of thalidomide analogues demonstrates the therapeutic efficacy of drug-induced degradation of transcription …