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. 2019 Apr;31:35-42.
doi: 10.1016/j.ddtec.2018.12.002. Epub 2019 Jan 14.

SNIPERs-Hijacking IAP Activity to Induce Protein Degradation

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SNIPERs-Hijacking IAP Activity to Induce Protein Degradation

Mikihiko Naito et al. Drug Discov Today Technol. .
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The induction of protein degradation by chimeric small molecules represented by proteolysis-targeting chimeras (PROTACs) is an emerging approach for novel drug development. We have developed a series of chimeric molecules termed specific and non-genetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs) that recruit IAP ubiquitin ligases to effect targeted degradation. Unlike the chimeric molecules that recruit von Hippel-Lindau and cereblon ubiquitin ligases, SNIPERs induce simultaneous degradation of IAPs such as cIAP1 and XIAP along with the target proteins. Because cancer cells often overexpress IAPs-a mechanism involved in the resistance to cancer therapy-SNIPERs could be used to kill cancer cells efficiently.

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