In vivo synthetic chemistry of proteolysis targeting chimeras (PROTACs)

Shusuke Tomoshige; Minoru Ishikawa

doi:10.1016/j.bmc.2021.116221

In vivo synthetic chemistry of proteolysis targeting chimeras (PROTACs)

Bioorg Med Chem. 2021 Jul 1:41:116221. doi: 10.1016/j.bmc.2021.116221. Epub 2021 May 19.

Authors

Shusuke Tomoshige¹, Minoru Ishikawa²

Affiliations

¹ Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan. Electronic address: stomoshi@tohoku.ac.jp.
² Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan.

PMID: 34034148
DOI: 10.1016/j.bmc.2021.116221

Abstract

Chemical knockdown of therapeutic targets using proteolysis targeting chimeras (PROTACs) is a rapidly developing field in drug discovery, but PROTACs are bifunctional molecules that generally show poor bioavailability due to their relatively high molecular weight. Recent developments aimed at the development of next-generation PROTACs include the in vivo synthesis of PROTAC molecules, and the exploitation of PROTACs as chemical tools for in vivo synthesis of ubiquitinated proteins. This short review covers recent advances in these areas and discusses the prospects for in vivo synthetic PROTAC technology.

Keywords: CLIPTACs; Chemical protein knockdown; In vivo synthetic chemistry; PROTACs; Ubiquitination.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Drug Discovery*
Humans
Molecular Targeted Therapy
Proteasome Endopeptidase Complex* / physiology
Proteolysis
Ubiquitin-Protein Ligases*

Substances

Proteasome Endopeptidase Complex
Ubiquitin-Protein Ligases