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ACS Chem Biol. 2017 Apr 21;12(4):892-898. doi: 10.1021/acschembio.6b01068. Epub 2017 Mar 20.

Proteolysis-Targeting Chimeras: Induced Protein Degradation as a Therapeutic Strategy.

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Department of Molecular, Cellular and Developmental Biology, ‡Department of Chemistry, and §Department of Pharmacology, Yale University , New Haven, Connecticut 06511, United States.


Until recently, the only ways to reduce specific protein signaling were to either knock down the target by RNAi or to interfere with the signaling by inhibiting an enzyme or receptor within the signal transduction cascade. Herein, we review an emerging class of small molecule pharmacological agents, called PROTACs, that present a novel approach to specifically target proteins and their respective signaling pathways. These heterobifunctional molecules utilize endogenous cellular quality control machinery by recruiting it to target proteins in order to induce their degradation.

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