SNIPERs—Hijacking IAP activity to induce protein degradation
Year: 2019
Type: review
Abstract: 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.
Institution: National Institute of Health Sciences
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,750
Awards: G2542793404, G2919372257, Development of novel anti-tumor drugs targeting the stability of oncogenic fusion kinase proteins, G3779320289, Manipulation of cellular function by forced ubiquitylation, G501204033, Development of small molecule chimeras that recruit a new E3 ligase to target proteins
OpenAlex ID: W2910045313