Small-molecule anticancer compounds selectively target the hemopexin domain of matrix metalloproteinase-9.

ABSTRACT: Lack of target specificity by existing matrix metalloproteinase (MMP) inhibitors has hindered antimetastatic cancer drug discovery. Inhibitors that bind to noncatalytic sites of MMPs and disrupt protease signaling function have the potential to be more specific and selective. In this work, compounds that target the hemopexin (PEX) domain of MMP-9 were identified using an in silico docking approach and evaluated using biochemical and biological approaches. Two of the selected compounds interfere with MMP-9-mediated cancer cell migration and proliferation in cells expressing exogenous or endogenous MMP-9. Furthermore, these inhibitors do not modulate MMP-9 catalytic activity. The lead compound, N-[4-(difluoromethoxy)phenyl]-2-[(4-oxo-6-propyl-1H-pyrimidin-2-yl)sulfanyl]-acetamide, specifical

SUBMITTER: Dufour A 

PROVIDER: S-EPMC3138841 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature