Format

Send to

Choose Destination
Drug Discov Today Technol. 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.

Author information

1
Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Japan. Electronic address: miki-naito@nihs.go.jp.
2
Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Japan.

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.

PMID:
31200857
DOI:
10.1016/j.ddtec.2018.12.002
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center