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:

Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, Hines J, Winkler JD, Crew AP, Coleman K, Crews CM
Chemistry & Biology 2015 22 1-9
Hines J, Grough JD, Corson TW, Crews C
Proc Natl Acad Sci U.S.A. 2013 110 22 8942-8947
Raina K, Crews CM
J. Biol. Chem. 2010 285 15 11057-11060
Rodriguez-Gonzalez A, Cyrus K, Salcius M, Kim K, Crews CM, Deshaeies RJ, Sakamoto KM
Oncogene 2008 27 57 7201-7211
Schnnekloth AR, Pucheault M, Tae HS, Crews CM
Bioorg. Med. Chem. Lett. 2008 18 22 5904-5908