Contents
Special Issue Topic

Proteolysis Targeting Chimera (PROTAC)

Guest Editor

Dr. Matthias Baud E-Mail

Lecturer in Medicinal Chemistry and Chemical Biology, University of Southampton, Southampton, UK

Research Keywords: Chemical biology; medicinal chemistry; small molecule; organic synthesis

About the Special lssue

Proteolysis targeting chimeras (PROTAC) are heterofunctional, bispecific molecules where two protein-binding probes are connected via a linker. The mechanism of action involves ternary complex formation in which one fragment interacts with the protein of interest (POI) and the other binds to a component of an ubiquitin ligase. This results in the poly-ubiquitination of the POI, which then undergoes proteasomal degradation, releasing the catalytic PROTAC. This strategy to reduce cellular protein levels has generated huge interest and excitement, and at present, there is significant research aimed at understanding the factors that determine functional efficiency. This is a truly exciting time for this field, which progressively shifted from a chemical biology concept to a new Eldorado for anticancer drug discovery. We feel that this special issue is particularly timely, and aims to provide an overview of the recent developments in the field of PROTAC, and applications to the development of novel candidate anticancer therapies.

In this issue, we welcome Original Articles and Reviews spanning from the molecular sciences to advanced clinical work. Critical aspects include the development of novel molecular design principles and synthetic strategies for assembling PROTACs, structural biology and the thermodynamics of ternary complexes, the identification of novel anticancer targets, and the evaluation of new PROTACs in cancer cells and animal studies. In addition, structure activity relationship (SAR) studies and the correlation of molecular structures and properties with overall biological activity and selectivity profiles in cellular/animal studies will present a particular interest, as we believe that much is still to be done to derive useful design criteria for the rational design and optimization of PROTACs.

Keywords: PROTAC; targeted anticancer therapy; induced protein degradation; ubiquitin-proteasome system; E3 ubiquitin ligase

Published Articles

Open Access Original Article
The bromodomain and extra-terminal domain degrader MZ1 exhibits preclinical anti-tumoral activity in diffuse large B-cell lymphoma of the activated B cell-like type
Chiara Tarantelli ... Francesco Bertoni
Published: December 31, 2021 Explor Target Antitumor Ther. 2021;2:586–601
4401 109 5
Open Access Review
The clinical advances of proteolysis targeting chimeras in oncology
Hao Xie ... Jason B. Fleming
Published: December 31, 2021 Explor Target Antitumor Ther. 2021;2:511–521
6604 237 25
Open Access Review
Proteolysis-targeting chimeras and their implications in breast cancer
Angeles C. Tecalco-Cruz ... Alberto Rojas-Ochoa
Published: December 31, 2021 Explor Target Antitumor Ther. 2021;2:496–510
4037 103 6
Open Access Review
Novel approaches for the rational design of PROTAC linkers
Almaz Zagidullin ... Emil Bulatov
Published: October 30, 2020 Explor Target Antitumor Ther. 2020;1:381–390
9568 517 40
Open Access Review
Current strategies for the design of PROTAC linkers: a critical review
Robert I. Troup ... Matthias G. J. Baud
Published: October 30, 2020 Explor Target Antitumor Ther. 2020;1:273–312
35519 3438 250
Open Access Review
PROTACs are effective in addressing the platelet toxicity associated with BCL-XL inhibitors
Peiyi Zhang ... Guangrong Zheng
Published: August 31, 2020 Explor Target Antitumor Ther. 2020;1:259–272
8819 341 19
Open Access Review
Development of PROTACs to address clinical limitations associated with BTK-targeted kinase inhibitors
Rachael Arthur ... Graham Packham
Published: June 29, 2020 Explor Target Antitumor Ther. 2020;1:131–152
9162 305 18