Daniel P. Bondeson

TL;DR: Major improvements to the proteolysis targeting chimeras (PROTACs) method are described, a chemical knockdown strategy in which a heterobifunctional molecule recruits a specific protein target to an E3 ubiquitin ligase, resulting in the target's ubiquitination and degradation.

TL;DR: A previously understudied benefit of small molecule proteolysis-targeting chimeras (PROTACs) that recruit E3 ubiquitin ligases to target proteins for their ubiquitination and subsequent proteasome-mediated degradation is reported.

TL;DR: The ability to target receptor tyrosine kinases for degradation using the PROTAC technology is demonstrated and the advantages of this degradation-based approach are outlined.

TL;DR: Recent advances in the use of small molecules to degrade proteins in a selective manner are reviewed to highlight all-small-molecule techniques with direct clinical application and describe techniques that may find broader acceptance in the biomedical research community that require little or no synthetic chemistry.

TL;DR: Together, these findings suggest that combined BCR-ABL1 kinase inhibition and protein degradation may represent a strategy to address B CR-ABl1-dependent drug resistance, and warrants further investigation into the eradication of persistent leukemic stem cells, which rely on neither the presence nor the activity of the BCR/F3 protein for survival.