title: Matrix metalloproteinase inhibitors: new challenges in the era of post broad-spectrum inhibitors.
abstract: More than two decades have been spent to develop many families of synthetic matrix metalloproteinases inhibitors (MMPI) as therapeutical agents for serious pathologies. Unfortunately, clinical trials conducted on broad-spectrum inhibitors have yielded disappointing results, especially in the cancer pathology area. Despite these outcomes, some small synthetic MMPI are in advanced trials or launched in clinical ones for cancer, arthritis, periodontal diseases. Today many groups are developing intensive efforts to find new classes of inhibitors characterized by improved potency and, above all, high selectivity against the specific MMP involved in each targeted pathology. The new challenges include the development of new MMPI bearing more effective ZBGs and the development of new allosteric non-zinc binding inhibitors, devoid of ZBGs. An analysis of more recent results in this field reported on journals and patents will be developed, to consider some of the more interesting new highly selective synthetic MMPI, their SARs, the new theoretical approaches used for modelling and the results of their biological evaluations.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nuti
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
mesh_terms: D000818:Animals; D001665:Binding Sites; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism
chemical_list: D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013449:Sulfonamides; D020782:Matrix Metalloproteinases; D015032:Zinc