Discovery of (S)-4-isobutyloxazolidin-2-one as a novel leucyl-tRNA synthetase (LRS)-targeted mTORC1 inhibitor

Suyoung Yoon, Jong Hyun Kim, Ina Yoon, Changhoon Kim, Sung Eun Kim, Yura Koh, Seung Jae Jeong, Jiyoun Lee, Sunghoon Kim, Jeewoo Lee

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16 Citations (Scopus)


A series of leucinol analogs were investigated as leucyl-tRNA synthetase-targeted mTORC1 inhibitors. Among them, compound 5, (S)-4-isobutyloxazolidin-2-one, showed the most potent inhibition on the mTORC1 pathway in a concentration-dependent manner. Compound 5 inhibited downstream phosphorylation of mTORC1 by blocking leucine-sensing ability of LRS, without affecting the catalytic activity of LRS. In addition, compound 5 exhibited cytotoxicity against rapamycin-resistant colon cancer cells, suggesting that LRS has the potential to serve as a novel therapeutic target.

Original languageEnglish
Pages (from-to)3038-3041
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number13
Publication statusPublished - 2016 Jul 1

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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