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

Suyoung Yoon; Jong Hyun Kim; Sung Eun Kim; Changhoon Kim; Phuong Thao Tran; Jihyae Ann; Yura Koh; Jayun Jang; Sungmin Kim; Hee Sun Moon; Won Kyung Kim; Sangkook Lee; Jiyoun Lee; Sunghoon Kim; Jeewoo Lee

doi:10.1021/acs.jmedchem.6b01190

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

Suyoung Yoon, Jong Hyun Kim, Sung Eun Kim, Changhoon Kim, Phuong Thao Tran, Jihyae Ann, Yura Koh, Jayun Jang, Sungmin Kim, Hee Sun Moon, Won Kyung Kim, Sangkook Lee, Jiyoun Lee, Sunghoon Kim, Jeewoo Lee

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

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.

Original language	English
Pages (from-to)	10322-10328
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	59
Issue number	22
DOIs	https://doi.org/10.1021/acs.jmedchem.6b01190
Publication status	Published - 23 Nov 2016

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/acs.jmedchem.6b01190

Cite this

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, 59(22), 10322-10328. https://doi.org/10.1021/acs.jmedchem.6b01190

@article{6bbd9ba853044708a38958a2860ddcd3,

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

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.",

author = "Suyoung Yoon and Kim, {Jong Hyun} and Kim, {Sung Eun} and Changhoon Kim and Tran, {Phuong Thao} and Jihyae Ann and Yura Koh and Jayun Jang and Sungmin Kim and Moon, {Hee Sun} and Kim, {Won Kyung} and Sangkook Lee and Jiyoun Lee and Sunghoon Kim and Jeewoo Lee",

note = "Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

year = "2016",

month = nov,

day = "23",

doi = "10.1021/acs.jmedchem.6b01190",

language = "English",

volume = "59",

pages = "10322--10328",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "22",

}

Yoon, S, Kim, JH, Kim, SE, Kim, C, Tran, PT, Ann, J, Koh, Y, Jang, J, Kim, S, Moon, HS, Kim, WK, 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, vol. 59, no. 22, pp. 10322-10328. https://doi.org/10.1021/acs.jmedchem.6b01190

TY - JOUR

T1 - Discovery of Leucyladenylate Sulfamates as Novel Leucyl-tRNA Synthetase (LRS)-Targeted Mammalian Target of Rapamycin Complex 1 (mTORC1) Inhibitors

AU - Yoon, Suyoung

AU - Kim, Jong Hyun

AU - Kim, Sung Eun

AU - Kim, Changhoon

AU - Tran, Phuong Thao

AU - Ann, Jihyae

AU - Koh, Yura

AU - Jang, Jayun

AU - Kim, Sungmin

AU - Moon, Hee Sun

AU - Kim, Won Kyung

AU - Lee, Sangkook

AU - Lee, Jiyoun

AU - Kim, Sunghoon

AU - Lee, Jeewoo

PY - 2016/11/23

Y1 - 2016/11/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84999752739&partnerID=8YFLogxK

U2 - 10.1021/acs.jmedchem.6b01190

DO - 10.1021/acs.jmedchem.6b01190

M3 - Article

C2 - 27933890

AN - SCOPUS:84999752739

SN - 0022-2623

VL - 59

SP - 10322

EP - 10328

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 22

ER -

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

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this