Activated leukocyte cell adhesion molecule (ALCAM) plays a relevant role in tumor biology and progression. Our previous studies showed that ALCAM is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form by ADAM-17-mediated shedding. This process is relevant toEOC cell motility and invasiveness, which is reduced by nonspecific inhibitors ofADAM-17. For this reason, ADAM-17 may represent a new useful target in anticancer therapy. Herein, we report the synthesis and biological evaluation of new ADAM-17 inhibitors containing an arylsulfonamidic scaffold. Among the new potential inhibitors, two very promising compounds 17 and 18 were discovered, with a nanomolar activity for ADAM-17 isolated enzyme. These compounds proved to be also the most potent in inhibiting soluble ALCAM release in cancer cells, showing a nanomolar activity on A2774 and SKOV3 cell lines.
|Autori:||NUTI E; CASALINI F; AVRAMOVA S I; SANTAMARIA S; FABBI M; FERRINI S; MARINELLI L; LA PIETRA V; LIMONGELLI V; NOVELLINO E; CERCIGNANI G; ORLANDINI E; NENCETTI S; ROSSELLO A|
|Titolo:||Potent Arylsulfonamide Inhibitors of Tumor Necrosis Factor-a Converting Enzyme Able to Reduce Activated Leukocyte Cell Adhesion Molecule Shedding in Cancer Cell Models|
|Anno del prodotto:||2010|
|Digital Object Identifier (DOI):||10.1021/jm901868z|
|Appare nelle tipologie:||1.1 Articolo in rivista|