Synthesis and discovery of the first potent proteolysis targeting chimaera (PROTAC) degrader of AIMP2-DX2 as a lung cancer drug
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 inh...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Book |
| Published: |
Taylor & Francis Group,
2023-12-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
MARC
| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_7b2ee4a801084b17b8b7db733202f13c | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a BoRa Lee |e author |
| 700 | 1 | 0 | |a Dae Gyu Kim |e author |
| 700 | 1 | 0 | |a Aram Lee |e author |
| 700 | 1 | 0 | |a Young Mi Kim |e author |
| 700 | 1 | 0 | |a Lianji Cui |e author |
| 700 | 1 | 0 | |a Sunghoon Kim |e author |
| 700 | 1 | 0 | |a Inhee Choi |e author |
| 245 | 0 | 0 | |a Synthesis and discovery of the first potent proteolysis targeting chimaera (PROTAC) degrader of AIMP2-DX2 as a lung cancer drug |
| 260 | |b Taylor & Francis Group, |c 2023-12-01T00:00:00Z. | ||
| 500 | |a 10.1080/14756366.2022.2135510 | ||
| 500 | |a 1475-6374 | ||
| 500 | |a 1475-6366 | ||
| 520 | |a 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. | ||
| 546 | |a EN | ||
| 690 | |a PROTAC | ||
| 690 | |a AIMP2-DX2 | ||
| 690 | |a lung cancer | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 38, Iss 1, Pp 51-66 (2023) | |
| 787 | 0 | |n https://www.tandfonline.com/doi/10.1080/14756366.2022.2135510 | |
| 787 | 0 | |n https://doaj.org/toc/1475-6366 | |
| 787 | 0 | |n https://doaj.org/toc/1475-6374 | |
| 856 | 4 | 1 | |u https://doaj.org/article/7b2ee4a801084b17b8b7db733202f13c |z Connect to this object online. |