Targeted Protein Degradation by Chimeric Small Molecules, PROTACs and SNIPERs

Mikihiko Naito; Nobumichi Ohoka; Norihito Shibata; Yoshinori Tsukumo

doi:10.3389/fchem.2019.00849

Targeted Protein Degradation by Chimeric Small Molecules, PROTACs and SNIPERs

Front Chem. 2019 Dec 10:7:849. doi: 10.3389/fchem.2019.00849. eCollection 2019.

Authors

Mikihiko Naito¹, Nobumichi Ohoka¹, Norihito Shibata¹, Yoshinori Tsukumo¹

Affiliation

¹ Laboratory Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Kawasaki, Japan.

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.

Publication types

Review