Matrix metalloprotease inhibitors MMPis

These compounds result in antiangiogenesis by inhibiting the matrix metalloproteases (zinc-dependent endopeptidases) of the extracellular matrix, thereby altering integrin-mediated cell adhesion. MMPis also promote local release of the proteoglycan-(membrane)-bound forms of VEGF, TNFa, and soluble Fas ligand. AG3340 is a potent, oral selective MMPi.

AG3340 (Prinomastat) was administered to 34 MDS patients of all subtypes in a phase II multicenter randomized trial.51 Patients were given either 5 mg or 15 mg daily and those who responded after 16 weeks were continued on therapy. Of 28 evaluable patients, 4 had major erythroid responses, with a median time to response of 12 weeks and median duration of response of 29+ weeks, being sustained for over a year after the end of treatment. The higher dose caused increased arthralgias and myalgias and the benefit appeared to be more significant in those patients with a lower risk disease.

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