jnj0966

Description: JNJ0966 is a novel, potent and highly selective allosteric inhibitor of MMP-9 (matrix metalloproteinase-9) zymogen with an IC50 of 440 nM. JNJ0966 inhibited activation of MMP-9 zymogen and subsequent generation of catalytically active enzyme. JNJ0966 had no effect on MMP-1, MMP-2, MMP-3, MMP-9, or MMP-14 catalytic activity and did not inhibit activation of the highly related MMP-2 zymogen. The molecular basis for this activity was characterized as an interaction of JNJ0966 with a structural pocket in proximity to the MMP-9 zymogen cleavage site near Arg-106, which is distinct from the catalytic domain. JNJ0966 was efficacious in reducing disease severity in a mouse experimental autoimmune encephalomyelitis model, demonstrating the viability of this therapeutic approach.

References: J Biol Chem. 2017 Oct 27; 292(43):17963-17974.