 When they were tested in patients they induced dose-limiting muscular and skeletal pain in a number of the patients.Only when the structures of the MMP inhibitors could be adjusted to impart selectivity and abolish toxicity, would they achieve clinical impact in cancer chemotherapy.The pioneering hydroxamate-based inhibitors were followed by a set of 'new generation' molecules with features including a substituted aryl, a sulfonamide and a hydroxamate zinc-binding group.