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10.1038/nrd.2016.211

http://scihub22266oqcxt.onion/10.1038/nrd.2016.211
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C5684876!5684876!27885283
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suck abstract from ncbi


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pmid27885283      Nat+Rev+Drug+Discov 2017 ; 16 (2): 101-14
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  • Induced protein degradation: an emerging drug discovery paradigm #MMPMID27885283
  • Lai AC; Crews CM
  • Nat Rev Drug Discov 2017[Feb]; 16 (2): 101-14 PMID27885283show ga
  • Small-molecule drug discovery has traditionally focused on occupancy of a binding site that directly affects protein function, which typically precludes targeting proteins that lack such amenable sites. Furthermore, high systemic drug exposures may be needed to maintain sufficient target inhibition in vivo, increasing the risk of undesirable off-target effects. Induced protein degradation is an alternative approach that is ?event-driven?: upon drug binding, the target protein is tagged for elimination. Emerging technologies based on proteolysis-targeting chimeras (PROTACs) that exploit cellular quality control machinery to selectively degrade target proteins are attracting considerable attention in the pharmaceutical industry owing to the advantages they could offer over traditional small-molecule strategies. These advantages include the potential to reduce systemic drug exposure, the ability to counteract increased target protein expression that often accompanies inhibition of protein function and the potential ability to target proteins that are not currently therapeutically tractable, such as transcription factors, scaffolding and regulatory proteins.



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