10.1021/acs.jmedchem.7b00228.s002
Qi Qi
Qi
Qi
Obiamaka Obianyo
Obiamaka
Obianyo
Yuhong Du
Yuhong
Du
Haian Fu
Haian
Fu
Shiyong Li
Shiyong
Li
Keqiang Ye
Keqiang
Ye
Blockade of Asparagine
Endopeptidase Inhibits Cancer
Metastasis
American Chemical Society
2017
AEP
breast cancer lung metastasis
represses breast cancer invasion
Asparagine Endopeptidase Inhibits Cancer Metastasis Asparagine endopeptidase
SAR
cancer treatment
inhibitor
MDA-MB -231 cells
MMP
cancer cell invasion
2017-08-17 21:04:57
Dataset
https://acs.figshare.com/articles/dataset/Blockade_of_Asparagine_Endopeptidase_Inhibits_Cancer_Metastasis/5324287
Asparagine endopeptidase (AEP), also
called legumain, is highly
expressed in various solid tumors, promoting cancer cell invasion,
migration, and metastasis. It has been proposed to be a prognostic
marker and therapeutic target for cancer treatment. However, an effective
nonpeptide, small-molecule inhibitor against this protease has not
yet been identified. Here we show that a family of xanthine derivatives
selectively inhibit AEP and suppress matrix metalloproteinase (MMP)
cleavage, leading to the inhibition of cancer metastasis. Through structure–activity
relationship (SAR) analysis, we obtained an optimized lead compound
(<b>38u</b>) that represses breast cancer invasion and migration.
Chronic treatment of nude mice, which had been inoculated with MDA-MB-231
cells, with inhibitor <b>38u</b> via oral administration robustly
inhibits breast cancer lung metastasis in a dose-dependent manner,
associated with blockade of MMP-2 by AEP. Therefore, our study supports
that <b>38u</b> might act as a potent and specific AEP inhibitor
useful for cancer treatment.