JNJ0966 is a highly selective [MMP-9 zymogen] inhibitor with an IC50 of 440 nM.

MMP9 zymogen:440 nM

The activations of proMMP-1, proMMP-2, and proMMP-3 are not significantly different in the presence or absence of 10 μM JNJ0966, whereas proMMP-9 activation by trypsin is significantly attenuated by JNJ0966. The addition of JNJ0966 to the reaction results in a significant reduction in fully processed MMP-9 and an apparent accumulation of the intermediate species[1].

JNJ0966 demonstrated effectiveness in alleviating the severity of disease in a mouse model of experimental autoimmune encephalomyelitis. Its effectiveness is dose-dependent, showing plasma and brain concentrations of 77.5±31.1 ng/mL (215 nM) and 481.6±162.5 ng/g (~1336 nM) at a 10-mg/kg dose, and 293.6±118.4 ng/mL (815 nM) in plasma and 1394.0±649.1 ng/g (~3867 nM) in the brain at a 30-mg/kg dose, respectively. Moreover, JNJ0966 exhibits a preference for accumulation in the brain, evidenced by brain/plasma ratios of 6.2 at the 10 mg/kg dose and 4.7 at the 30 mg/kg dose.