Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy

Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand (mostly small-molecule inhibitor) of the protein of interest (POI) and a covalently linked ligand of an E3 ubiquitin ligase (E3). Upon binding to the POI, the PROTAC can recruit E3 for POI ubiquitination, which is subjected to proteasome-mediated degradation. PROTAC complements nucleic acid-based gene knockdown/out technologies for targeted protein reduction and could mimic pharmacological protein inhibition. To date, PROTACs targeting ~ 50 proteins, many of which are clinically validated drug targets, have been successfully developed with…

• UD
  U.S. Department of Defense

  Awards: RP180177, W81XWH, W81XWH-18-1-0368, W81XWH-18
• CP
  Cancer Prevention and Research Institute of Texas

  Awards: RP180177, RP150129
• UA
  U.S. Army Medical Research Acquisition Activity

  Award: W81XWH-18-1-0368