IKZF2 Degradation: It′s Time to Take into Account it When Designing Cereblon‐Based PROTACs

Author:

Li Minglei12ORCID

Affiliation:

1. Chemical Biology Center School of Pharmaceutical Sciences & Institute of Materia Medical Shandong First Medical University & Shandong Academy of Medical Sciences Jinan 250117 Shandong China

2. School of Pharmaceutical Sciences & Institute of Materia Medical Shandong First Medical University & Shandong Academy of Medical Sciences National Key Laboratory of Advanced Drug Delivery System Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences) Key Lab for Rare & Uncommon Diseases of Shandong Province Jinan 250117 Shandong China

Abstract

AbstractProteolysis‐targeting chimera (PROTAC) has become a very important means of protein degradation and a new way of disease treatment. In particular, PROTACs constructed with ligands for E3 ligase cereblon account for more than 90 % of the PROTACs currently in clinical research. Notably, CRBN ligands themselves are a class of molecular glue compounds capable of degrading neo‐substrate proteins. Compared to the target proteins degradation, the degradation of neo‐substrates, especially IKZF2, has not received enough attention. Therefore, this review summarizes the currently published IKZF2 degraders derived from articles and patents, which are conducive to the design of PROTACs with desired IKZF2 degradation from the perspective of medicinal chemistry.

Funder

Postdoctoral Innovation Project of Shandong Province

Publisher

Wiley

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