当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > A novel NAE/UAE dual inhibitor LP0040 blocks neddylation and ubiquitination leading to growth inhibition and apoptosis of cancer cells.

A novel NAE/UAE dual inhibitor LP0040 blocks neddylation and ubiquitination leading to growth inhibition and apoptosis of cancer cells.

Abstract：

:NEDD8 activating enzyme (NAE) plays an important role in regulating intracellular proteins with key parts in a broad array of cellular functions. On the basis of previously work, a series of 2H-chromen-2-one based NAE inhibitors were designed and synthesized. Through enzyme-based and cell-based assays, LP0040 was identified as a non-nucleoside NAE/UAE dual inhibitor. It could inhibit NAE/UAE activities and downregulated degradations of related substrates in AGS cells, promoting apoptosis in low micromole concentrations. LP0040 possessed anti-proliferation activities with IC50 values of 0.76-3.29 μM against multiple human cancer lines and had synergistic effect with bortezomib. Thus LP0040 represented valuable starting points for future development of NAE/UAE dual inhibitors.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Lu P,Guo Y,Zhu L,Xia Y,Zhong Y,Wang Y

doi

10.1016/j.ejmech.2018.05.027

subject

Has Abstract

pub_date

2018-06-25 00:00:00

pages

294-304

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(18)30437-9

journal_volume

154

pub_type

杂志文章

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