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Description

A dibenzofuranylsulfanamido-valine compound that acts as a potent, active site zinc-targeting, MMP-12-selective inhibitor (IC = 2 nM against human MMP-12) with much weaker activity against MMP-12 from mouse/rat/sheep species (IC = 160, 320 and 22.3 nM, respectively) or human MMP-3/13/14 (IC = 351, 120 and 1100 nM , respectively), and practically ineffective toward human Agg-1/2 (IC >5 microM), TACE (IC >25 microM), and MMP-1/7 (IC >6 microM). MMP408 is orally active in mice and shown to effectively alleviate rhMMP-12-induced pulmonary inflammatory response in mice in vivo by more than 50% (5 mg/kg, p.o., b.i.d.)., A dibenzofuranylsulfanamido-valine compound that acts as a potent, active site zinc-targeting, MMP-12-selective inhibitor (IC = 2 nM against human MMP-12) with much weaker activity against MMP-12 from mouse/rat/sheep species (IC = 160, 320 and 22.3 nM , respectively) or human MMP-3/13/14 (IC = 351, 120 and 1100 nM , respectively), and practically ineffective toward human Agg-1/2 (IC >5 microM), TACE (IC >25 microM), and MMP-1/7 (IC >6 microM). MMP408 is orally active in mice and shown to effectively alleviate rhMMP-12-induced pulmonary inflammatory response in mice in vivo by more than 50% (5 mg/kg, p.o., b.i.d.).