2. Academic Validation
  3. Discovery of benzodioxane analogues as lead candidates of AIMP2-DX2 inhibitors

Discovery of benzodioxane analogues as lead candidates of AIMP2-DX2 inhibitors

  • Bioorg Med Chem Lett. 2022 Oct 1;73:128889. doi: 10.1016/j.bmcl.2022.128889.
BoRa Lee 1,  Dae Gyu Kim 2,  Young Mi Kim 1,  Sunghoon Kim 3,  Inhee Choi 4
Affiliations

Affiliations

  • 1 Medicinal Chemistry, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea.
  • 2 Medicinal Bioconvergence Research Center, Institute for Artificial Intelligence and Biomedical Research, College of Pharmacy & College of Medicine, Interdisciplinary Biomedical Center, Gangnam Severance Hospital, Yonsei University, Korea.
  • 3 Medicinal Bioconvergence Research Center, Institute for Artificial Intelligence and Biomedical Research, College of Pharmacy & College of Medicine, Interdisciplinary Biomedical Center, Gangnam Severance Hospital, Yonsei University, Korea. Electronic address: sunghoonkim@yonsei.ac.kr.
  • 4 Medicinal Chemistry, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea. Electronic address: inhee.choi@ip-korea.org.
PMID: 35842206 DOI: 10.1016/j.bmcl.2022.128889
Abstract

Aminoacyl-tRNA Synthetase (ARS) interacting multifunctional protein2 (AIMP2) plays a vital role in protein synthesis. However, a splicing variant in which the second of the four exons of AIMP2 is deleted, inhibits the tumor suppression activity of AIMP2. Herein, we describe our discovery of series of potent AIMP2-DX2 inhibitors that are targeting lung Cancer. Optimization of series using ligand-based drug design strategy led to discovery of compound 35, a potent AIMP2-DX2 inhibitor that is the most efficacious in H460 and A549 cells. This benzodioxane series may represent good starting points for further lead optimization of the identification potential drug candidates for the AIMP2-DX2 targeted treatment of lung Cancer.

Keywords

AIMP2-DX2; Ligand-based drug design; Lung cancer; SAR.

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