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The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Discovery of simplified leucyladenylate sulfamates as novel leucyl-tRNA synthetase (LRS)-targeted mammalian target of rapamycin complex 1 (mTORC1) inhibitors

Yoon, Suyoung, Kim, Jong Hyun, Koh, Yura, Tran, Phuong-Thao, Ann, Jihyae, Yoon, Ina, Jang, Jayun, Kim, Won Kyung, Lee, Sangkook, Lee, Jiyoun, Kim, Sunghoon, Lee, Jeewoo·2017·Bioorganic & Medicinal Chemistry
DOI 10.1016/j.bmc.2017.06.002
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Abstract

Leucyl-tRNA synthetase (LRS) has been reported to be a possible mediator of intracellular amino acids signaling to mTORC1. Given that mTORC1 is associated with cell proliferation and tumorigenesis, the LRS-mediated mTORC1 pathway may offer an alternative strategy in anticancer therapy. In this study, we developed a series of simplified analogues of leucyladenylate sulfamate (1) as LRS-targeted mTORC1 inhibitors. We replaced the adenylate group with a N-(3,4-dimethoxybenzyl)benzenesulfonamide (2a) or a N-(2-phenoxyethyl)benzenesulfonamide groups (2b) that can maintain specific binding, but has more favorable physicochemical properties such as reduced polarity and asymmetric centers. Among these simplified analogues, compound 16 and its constrained analogue 22 effectively inhibited S6K phosphorylation in a dose-dependent manner and exhibited cancer cell specific cytotoxicity against six different types of cancer cells. This result supports that LRS is a viable target for novel anticancer therapy.

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Research works printed but not linked: 20

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Metadata

Authors
Yoon, S., Kim, J. H., Koh, Y., Tran, P.-T., Ann, J., Yoon, I., Jang, J., Kim, W. K., Lee, S., Lee, J., Kim, S., & Lee, J.
ORCID
Kim, Jong Hyun
Venue
Bioorganic & Medicinal Chemistry
Publisher
Elsevier BV
Published
2017-08
Volume
25
Issue
15
Pages
4145-4152
ISSN
0968-0896
DOI
10.1016/j.bmc.2017.06.002
Cited by
15
References
1
Language
en
Licence
Funders
Ministry of Education, Science and Technology of Korea (NRF-2012M3A6A4054928)

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