当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Structure-activity relationship of leucyladenylate sulfamate analogues as leucyl-tRNA synthetase (LRS)-targeting inhibitors of Mammalian target of rapamycin complex 1 (mTORC1).

Structure-activity relationship of leucyladenylate sulfamate analogues as leucyl-tRNA synthetase (LRS)-targeting inhibitors of Mammalian target of rapamycin complex 1 (mTORC1).

Abstract：

:Leucyl-tRNA synthetase (LRS) plays an important role in amino acid-dependent mTORC1 signaling, which is known to be associated with cellular metabolism and proliferation. Therefore, LRS-targeting small molecules that can suppress mTORC1 activation may provide an alternative strategy to current anticancer therapy. In this work, we developed a library of leucyladenylate sulfate analogues by extensively modifying three different pharmacophoric regions comprising adenine, ribose and leucine. Several effective compounds were identified by cell-based mTORC1 activation assays and further tested for anticancer activity. The selected compounds mostly exhibited selective cytotoxicity toward five different cancer cell lines, supporting the hypothesis that the LRS-mediated mTORC1 pathway is a promising alternative target to current therapeutic approaches.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Yoon S,Kim SE,Kim JH,Yoon I,Tran PT,Ann J,Kim C,Byun WS,Lee S,Kim S,Lee J,Lee J

doi

10.1016/j.bmc.2019.01.037

subject

Has Abstract

pub_date

2019-03-15 00:00:00

pages

1099-1109

issue

6

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(18)32164-3

journal_volume

27

pub_type

杂志文章

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