PROTACs (Proteolysis Targeting Chimera)

Recruiting Targeted Proteins to E3 Ligases to Induce their Degradation

For the past several years, we have demonstrated the feasibility of controlling intracellular protein levels by recruiting targeted proteins to E3 ligases to induce their ubiquitination and subsequent proteasome mediated degradation.  This heterodimeric approach has proven successful for a variety of E3 ubiquitin ligases and targeted proteins.  Current efforts to develop clinical drug candidates using this technology are underway in collaboration with GlaxoSmithKline.

Relevant Publications:

Corson TW, Aberle N, Crews CM
ACS Chemical Biology 2008 3 11 677-692
Sakamoto KM, Kim K, Verma R, Ransick A, Stein B, Crews CM, Deshaies RJ
Mol Cell Proteomics 2003 2 12 1350-1358
Sakamoto KM, Kim KB, Kumagai A, Mercurio F, Crews CM, Deshaies RJ
Proc. Natl. Acad. Sci. USA 2001 98 15 8554-8559