ARS-interacting multifunctional proteins 2 (AIMP2) is known to be a powerful tumour suppressor. However, the target AIMP2-DX2, AIMP2-lacking exon 2, is often detected in many cancer patients and cells. The predominant approach for targeting AIMP-DX2 has been attempted via small molecule mediated inhibition, but due to the lack of satisfactory activity against AIMP2-DX2, new therapeutic strategies are needed to develop a novel drug for AIMP2-DX2. Here, we report the use of the PROTAC strategy that combines small-molecule AIMP2-DX2 inhibitors with selective E3-ligase ligands with optimised linkers. Consequently, candidate compound 45 was found to be a degrader of AIMP2-DX2. Together, these findings demonstrate that our PROTAC technology targeting AIMP2-DX2 would be a potential new strategy for future lung cancer treatment.
|Number of pages||16|
|Journal||Journal of Enzyme Inhibition and Medicinal Chemistry|
|Publication status||Published - 2023|
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) under Grant NRF-2017M3A9G6068257, 2021R1A3B1076605; and the Yonsei University Research Fund under Grant 2021–22-0061, 0291, and 0293.
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
All Science Journal Classification (ASJC) codes
- Drug Discovery