The state of the art of PROTAC technologies for drug discovery

Chao Wang; Cangxin Zheng; Han Wang; Liangren Zhang; Zhenming Liu; Ping Xu

doi:10.1016/j.ejmech.2022.114290

The state of the art of PROTAC technologies for drug discovery

Eur J Med Chem. 2022 May 5:235:114290. doi: 10.1016/j.ejmech.2022.114290. Epub 2022 Mar 15.

Authors

Chao Wang¹, Cangxin Zheng², Han Wang², Liangren Zhang³, Zhenming Liu³, Ping Xu⁴

Affiliations

¹ National Pharmaceutical Teaching Laboratory Center, School of Pharmaceutical Sciences, Peking University, Beijing, China.
² Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University, Beijing, China.
³ Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University, Beijing, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
⁴ Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University, Beijing, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China. Electronic address: pingxu@bjmu.edu.cn.

PMID: 35307618
DOI: 10.1016/j.ejmech.2022.114290

Abstract

Protein degradation technology has progressed dramatically since 2001 when proteolysis targeting chimera (PROTAC) was first reported. Various of distinctive degradation technologies based on PROTAC have been developed for the degradation of kinases, nuclear receptors, epigenetic proteins, misfolded proteins, and also RNAs, etc. These technologies greatly broaden the spectrum of targets and the scope of clinical applications for the treatment of cancer, neurodegenerative diseases and virus diseases, etc. More than 15 targeted degraders have been in the clinic to date. Here in this review, we summarized the constituents and examples of different degradation strategies, as well as their advantages and limitations.

Keywords: AbTAC; CHAMP; CLIPTAC; Degradation; Molecular glue; PHOTAC; PROTAC; RIBOTAC; SPNpro; TF-PROTAC; antibody-PROTAC conjugate; bioPROTAC; floate-PROTAC.

Publication types

Review

MeSH terms

Drug Discovery*
Proteolysis*
Technology