Potent arylsulfonamide inhibitors of tumor necrosis factor-alpha converting enzyme able to reduce activated leukocyte cell adhesion molecule shedding in cancer cell models.

Article Details

Citation

Copy to clipboard

Nuti E, Casalini F, Avramova SI, Santamaria S, Fabbi M, Ferrini S, Marinelli L, La Pietra V, Limongelli V, Novellino E, Cercignani G, Orlandini E, Nencetti S, Rossello A

Potent arylsulfonamide inhibitors of tumor necrosis factor-alpha converting enzyme able to reduce activated leukocyte cell adhesion molecule shedding in cancer cell models.

J Med Chem. 2010 Mar 25;53(6):2622-35. doi: 10.1021/jm901868z.

PubMed ID

20180536 [ View in PubMed

]

Abstract

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 to EOC cell motility and invasiveness, which is reduced by nonspecific inhibitors of ADAM-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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
CGS-27023	Interstitial collagenase	IC 50 (nM)	56	N/A	N/A	Details