Tumor-induced bone disease is a common clinical feature of certain cancers such as breast, prostate, and lung carcinomas, for which the incidence of bone metastases can be 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. MMP inhibitors can disrupt the cycle of bone matrix turnover and tumor cell growth, and are thus potential therapeutic agents for certain bone diseases.

Paolo Tortorella and team, 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, the team arrived at a potent MMP inhibitor that also shows very good in vitro anti-resorptive activity. This compound is a good lead for developing new agents for treating tumor-induced bone disease characterized by increased osteoclast activity.

• Biphenyl Sulfonylamino Methyl Bisphosphonic Acids as Inhibitors of Matrix Metalloproteinases and Bone Resorption
  M. T. Rubino, M. Agamennone, C. Campestre, P. Campiglia, V. Cremasco et al.,
  ChemMedChem 2011, 6 (7).
  DOI: 10.1002/cmdc.201000540