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

Yoon, Suyoung, Kim, Jong Hyun, Yoon, Ina, Kim, Changhoon, Kim, Sung-Eun, Koh, Yura, Jeong, Seung Jae, Lee, Jiyoun, Kim, Sunghoon, Lee, Jeewoo·2016·Bioorganic & Medicinal Chemistry Letters
DOI 10.1016/j.bmcl.2016.05.011
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Abstract

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.

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Metadata

Authors
Yoon, S., Kim, J. H., Yoon, I., Kim, C., Kim, S.-E., Koh, Y., Jeong, S. J., Lee, J., Kim, S., & Lee, J.
ORCID
Venue
Bioorganic & Medicinal Chemistry Letters
Publisher
Elsevier BV
Published
2016-07
Volume
26
Issue
13
Pages
3038-3041
ISSN
0960-894X
DOI
10.1016/j.bmcl.2016.05.011
Cited by
19
References
2
Language
en
Licence
Funders
National Research Foundation (NRF-2012M3A6A4054928)

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