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SNIPERs-Hijacking IAP activity to induce protein degradation.

Drug discovery today. Technologies (2019-06-16)
Mikihiko Naito, Nobumichi Ohoka, Norihito Shibata
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
A1V2PF2-NHEt-PEG3-NH2, ≥95%
Sigma-Aldrich
BocA1V1PF2-OC6-NH2 hydrochloride, ≥95%
Sigma-Aldrich
BocA1V2PF1-NHPEG1-NH2
Sigma-Aldrich
A1V1PF2-OEt-PEG1-NH2 hydrochloride
Sigma-Aldrich
A1V1PF2-OEt-PEG3-NH2 hydrochloride
Sigma-Aldrich
A1V2PF1-NHEt-C10-NH2
Sigma-Aldrich
A1V2PF2-NHEt-C6-NH2
Sigma-Aldrich
A1V2PF1-NHEt-C6-NH2
Sigma-Aldrich
A1V2PF1-NHEt-PEG3-NH2
Sigma-Aldrich
A1V2PF1-NHEt-PEG1-NH2, ≥95%
Sigma-Aldrich
BocA1V1PF2-OC10-NH2 hydrochloride
Sigma-Aldrich
A1V2PF2-NHEt-C10-NH2, ≥95%
Sigma-Aldrich
BocA1V2PF2-NHPEG3-NH2, ≥95%
Sigma-Aldrich
A1V1PF2-OEt-C6-NH2 hydrochloride
Sigma-Aldrich
BocA1V2PF2-NHC10-NH2, ≥85%
Sigma-Aldrich
BocA1V2PF2
Sigma-Aldrich
BocA1V2PF2-NHC6-NH2
Sigma-Aldrich
BocA1V2PF2-NHPEG1-NH2
Sigma-Aldrich
ComInnex IAP Ligand Library
Sigma-Aldrich
A1V2PF2-NHEt, ≥95%
Sigma-Aldrich
A1V2PF2-NHEt-PEG1-NH2
Sigma-Aldrich
A1V1PF2-OEt-C10-NH2 hydrochloride
Sigma-Aldrich
BocA1V2PF1-NHC10-NH2
Sigma-Aldrich
BocA1V1PF2-OPEG1-NH2 hydrochloride, ≥95%
Sigma-Aldrich
BocA1V2PF1, ≥95%
Sigma-Aldrich
A1V1PF2-OEt, ≥95%
Sigma-Aldrich
BocA1V1PF2, ≥95%
Sigma-Aldrich
BocA1V1PF2-OPEG3-NH2 hydrochloride
Sigma-Aldrich
BocA1V2PF1-NHC6-NH2
Sigma-Aldrich
BocA1V2PF1-NHPEG3-NH2, ≥85%