Kazuki Yamamoto
Pharmacia, 2023, 59(10), 943
https://doi.org/10.14894/faruawpsj.59.10_943

Abstract

Unlike conventional inhibitors, which bind to target proteins and reduce their function, proteolysis inducers are attracting attention as new drug discovery modalities because they chemically knock down target proteins. Proteolysis targeting chimera (PROTAC) has an E3 ligase and a binding site for the target molecule in its molecule, and induces degradation by forcibly ubiquitinating the target protein. One of the advantages of PROTAC is that it acts catalytically, and lower doses can be expected to reduce toxicity. However, in the development of PROTACs, there are no guidelines for optimizing the modification position of the target binder or the length and shape of the linker, and it is necessary to customize it depending on the target, so efficiency is required. This time, we will introduce an approach to PROTAC optimization using Chen et al.'s DNA encoded library (DEL).