Although many kinds of therapies are applied in the clinic, drug-resistance is a major and unavoidable problem. Another disturbing statistic is the limited number of drug targets, which are presently only 20–25% of all protein targets that are currently being studied. Moreover, the focus of current explorations of targets are their enzymatic functions, which ignores the functions from their scaffold moiety. As a promising and appealing technology, PROteolysis TArgeting Chimeras (PROTACs) have attracted great attention both from academia and industry for finding available approaches to solve the above problems. PROTACs regulate protein function by degrading target proteins instead of inhibiting them, providing more sensitivity to drug-resistant targets and a greater chance to affect the nonenzymatic functions. PROTACs have been proven to show better selectivity compared to classic inhibitors. PROTACs can be described as a chemical knockdown approach with rapidity and reversibility, which presents new and different biology compared to other gene editing tools by avoiding misinterpretations that arise from potential genetic compensation and/or spontaneous mutations. PRTOACs have been widely explored throughout the world and have outperformed not only in cancer diseases, but also in immune disorders, viral infections and neurodegenerative diseases. Although PROTACs present a very promising and powerful approach for crossing the hurdles of present drug discovery and tool development in biology, more efforts are needed to gain to get deeper insight into the efficacy and safety of PROTACs in the clinic. More target binders and more E3 ligases applicable for developing PROTACs are waiting for exploration.

PROTACs: great opportunities for academia and industry.

A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry.

Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities.

Contemporary Challenges in the Design of Topoisomerase II Inhibitors for Cancer Chemotherapy

Quinazolines and quinazolinones as ubiquitous structural fragments in medicinal chemistry: An update on the development of synthetic methods and pharmacological diversification

Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC).

Small molecule selenium-containing compounds: Recent development and therapeutic applications.

Discovery of potent small molecule PROTACs targeting mutant EGFR.

Synthesis and anticancer activity evaluation of a series of [1,2,4]triazolo[1,5-a]pyridinylpyridines in vitro and in vivo.

Discovery of novel 9-heterocyclyl substituted 9H-purines as L858R/T790M/C797S mutant EGFR tyrosine kinase inhibitors

San-Qi Zhang

Papers

Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC).

Small molecule selenium-containing compounds: Recent development and therapeutic applications.

Discovery of potent small molecule PROTACs targeting mutant EGFR.

Synthesis and anticancer activity evaluation of a series of [1,2,4]triazolo[1,5-a]pyridinylpyridines in vitro and in vivo.

Discovery of novel 9-heterocyclyl substituted 9H-purines as L858R/T790M/C797S mutant EGFR tyrosine kinase inhibitors