Annual review of PROTAC degraders as anticancer agents in 2022.

Eur J Med Chem

School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China; State Key Laboratory of Esophageal Cancer Prevention &Treatment, Zhengzhou 450001, China. Electronic address:

Published: March 2024

Following nearly two decades of development, significant advancements have been achieved in PROTAC technology. As of the end of 2022, more than 20 drugs have entered clinical trials, with ARV-471 targeting estrogen receptor (ER) showing remarkable progress by entering phase III clinical studies. In 2022, significant progress has been made on multiple targets. The first reversible covalent degrader designed to target the KRAS mutant protein, based on cyclopropionamide, has been reported. Additionally, the activity HDCA1 degrader surpassed submicromolar levels during the same year. A novel FEM1B covalent ligand called EN106 was also discovered, expanding the range of available ligands. Furthermore, the first PROTAC drug targeting SOS1 was reported. Additionally, the first-in-class degraders that specifically target BRD4 isoforms (BRD4 L and BRD4 S) have recently been reported, providing a valuable tool for further investigating the biological functions of these isoforms. Lastly, a breakthrough was also achieved with the first degrader targeting both CDK9 and Cyclin T1. In this review, we aimed to update the PROTAC degraders as potential anticancer agents covering articles published in 2022. The design strategies, degradation effects, and anticancer activities were highlighted, which might provide an updated sight to develop novel PROTAC degraders with great potential as anticancer agents as well as favorable drug-like properties.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2024.116166DOI Listing

Publication Analysis

Top Keywords

protac degraders
12
anticancer agents
12
reported additionally
8
potential anticancer
8
protac
5
annual review
4
review protac
4
degraders
4
anticancer
4
degraders anticancer
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!