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Discovery of Leucyladenylate Sulfamates as Novel Leucyl-tRNA Synthetase (LRS)-Targeted Mammalian Target of Rapamycin Complex 1 (mTORC1) Inhibitors

Yoon, Suyoung, Kim, Jong Hyun, Kim, Sung-Eun, Kim, Changhoon, Tran, Phuong-Thao, Ann, Jihyae, Koh, Yura, Jang, Jayun, Kim, Sungmin, Moon, Hee-sun, Kim, Won Kyung, Lee, Sangkook, Lee, Jiyoun, Kim, Sunghoon, Lee, Jeewoo·2016·Journal of Medicinal Chemistry
DOI 10.1021/acs.jmedchem.6b01190
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Abstract

Recent studies indicate that LRS may act as a leucine sensor for the mTORC1 pathway, potentially providing an alternative strategy to overcome rapamycin resistance in cancer treatments. In this study, we developed leucyladenylate sulfamate derivatives as LRS-targeted mTORC1 inhibitors. Compound 18 selectively inhibited LRS-mediated mTORC1 activation and exerted specific cytotoxicity against colon cancer cells with a hyperactive mTORC1, suggesting that 18 may offer a novel treatment option for human colorectal cancer.

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Metadata

Authors
Yoon, S., Kim, J. H., Kim, S.-E., Kim, C., Tran, P.-T., Ann, J., Koh, Y., Jang, J., Kim, S., Moon, H.-S., Kim, W. K., Lee, S., Lee, J., Kim, S., & Lee, J.
Affiliations
  • Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
  • Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
  • Department of Global Medical Science, Sungshin University, Seoul 142-732, Korea
Venue
Journal of Medicinal Chemistry
Publisher
American Chemical Society (ACS)
Published
2016-11-09
Volume
59
Issue
22
Pages
10322-10328
ISSN
  • 0022-2623
  • 1520-4804
DOI
10.1021/acs.jmedchem.6b01190
Cited by
17
References
1
Language
en
Funders
National Research Foundation of Korea (NRF-2012M3A6A4054928)

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CoChat. (2026). Citation check: Discovery of Leucyladenylate Sulfamates as Novel Leucyl-tRNA Synthetase (LRS)-Targeted Mammalian Target of Rapamycin Complex 1 (mTORC1) Inhibitors. https://app.cochat.ai/papers/10.1021/acs.jmedchem.6b01190
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Yoon, S., Kim, J. H., Kim, S.-E., Kim, C., Tran, P.-T., Ann, J., Koh, Y., Jang, J., Kim, S., Moon, H.-S., Kim, W. K., Lee, S., Lee, J., Kim, S., & Lee, J. (2016). Discovery of Leucyladenylate Sulfamates as Novel Leucyl-tRNA Synthetase (LRS)-Targeted Mammalian Target of Rapamycin Complex 1 (mTORC1) Inhibitors. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.6b01190