 It showed excellent preclinical animal anticancer efficacy, but a recurring limitation to these hydroxamates (Prinomastat in particular) is drug metabolism including loss of the hydroxamate zinc-binding group.These inhibitors were followed by the next group of hydroxamate-based inhibitors, which focus on the suppression of metabolism, minimization of MMP-1 inhibitory activity and the control of subtype selectivity, by structure-based design.The tetrahydropyran in RS-130830 introduces a steric block that suppresses metabolism, which would fix the problem that the previous generation of inhibitors showed.