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Review
. 2019 Dec 10;7:849.
doi: 10.3389/fchem.2019.00849. eCollection 2019.

Targeted Protein Degradation by Chimeric Small Molecules, PROTACs and SNIPERs

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Free PMC article
Review

Targeted Protein Degradation by Chimeric Small Molecules, PROTACs and SNIPERs

Mikihiko Naito et al. Front Chem. .
Free PMC article

Abstract

Technologies that induce targeted protein degradation by small molecules have been developed recently. Chimeric small molecules such as Proteolysis Targeting Chimeras (PROTACs) and Specific and Non-genetic IAP-dependent Protein Erasers (SNIPERs), and E3 modulators such as thalidomides, hijack the cellular machinery for ubiquitylation, and the ubiquitylated proteins are subjected to proteasomal degradation. This has motivated drug development in industry and academia because "undruggable targets" can now be degraded by targeted protein degradation.

Keywords: E3 modulator; PROTAC; SNIPER; proteasome; protein degradation; ubiquitin.

Figures

Figure 1
Figure 1
Classification of degrader molecules.
Figure 2
Figure 2
Chemical structure of the E3 ligands (A), and the E3 ligase complexes hijacked by chimeric degraders (B).

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