Cover image for Vol. 11 Issue 12

Editorial Board Chairs: Antonello Mai, Rainer Metternich. Assoc. Editors: David Peralta, Scott Williams (Sr)

Impact Factor: 2.968

ISI Journal Citation Reports © Ranking: 2014: 19/59 (Chemistry Medicinal); 83/255 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

March 16, 2011

VIP: Biphenyl Sulfonylamino Methyl Bisphosphonic Acids as Inhibitors of Matrix Metalloproteinases and Bone Resorption

VIP: Biphenyl Sulfonylamino Methyl Bisphosphonic Acids as Inhibitors of Matrix Metalloproteinases and Bone ResorptionMaria Teresa Rubino, Mariangela Agamennone, Cristina Campestre, Pietro Campiglia, Viviana Cremasco, Roberta Faccio, Antonio Laghezza, Fulvio Loiodice, Dariana Maggi, Emilia Panza, Armando Rossello, and Paolo Tortorella*

Tumor-induced bone disease is a common clinical feature of certain cancers, including breast, prostate, and lung carcinomas, for which the likelihood of developing bone metastases increases considerably with an incidence as high as 70%. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that catalyze the turnover of extracellular matrix components and play a critical role in cancer metastasis. A number of MMPs are also involved in the balance of bone remodeling and in bone matrix turnover associated with the presence of cancer cells. MMP inhibitors may disrupt the cycle of bone matrix turnover and tumor cell growth, thus acting as potential therapeutic agents for certain bone diseases.

In this context, a collaborative research team led by Paolo Tortorella (Università degli Studi “Aldo Moro”, Bari, Italy) designed a series of MMP inhibitors characterized by a bisphosphonate moiety, a well-known bone-seeking agent, as a zinc binding group. After lead optimization, Tortorella and colleagues arrived at a very potent MMP inhibitor that also shows very good in vitro anti-resorptive activity. This compound is considered to be a good lead for the development of new therapeutic agents in the treatment of tumor-induced bone disease characterized by increased osteoclast activity.

Received December 14, 2010; published online March 15, 2011, DOI: 10.1002/cmdc.201000540.

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