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:

Raina K, Lu J, Qian Y, Altieri M, Gordon D, Rossi AMK, Wang J, Chen X, Dong H, Siu K, Winkler JD, Crew AP, Crews CM, and Coleman KG
Proc Natl Acad Sci, USA 2016
Toure M, Crews CM
Angewandte Chemie International Edition 2016 55 2-10
Lai AC, Toure M, Hellerschmied D, Salami J, Jaime-Figueroa S, Ko E, Hines J, Crews CM
Angewandte Chemie International Edition 2016 55 2 807-810
Buckley DL, Raina K, Darricarrerre N, Hines J, Gustafson JL, Smith IE, Miah AH, Harling JD, Crews CM
ACS Chemical Biology 2015 doi:10.1021/acschembio.5b00442
Bondeson DP, Mares A, Smith IED, Ko E, Campos S, Miah AH, Mulholland KE, Routly N, Buckley DL, Gustafson JL, Zinn N, Grandi P, Shimamura S, Bergamini G, Faelth-Savitski M, Bantscheff M, Cox C, Gordon DA, Willard RR, Flanagan JJ, Casillas LN, Votta BJ, den Besten W, Famm K, Sruidenier L, Carter PS, Harling JD, Churcher I, & Crews CM
Nature Chemical Biology 2015 doi:10.1038/nchembio. 1858