Matrix metalloproteinases (MMP) are a family of proteolytic enzymes that participate in tissue remodeling and molecular signaling. MMP-9, a member of the MMP family, is excessively expressed in many human diseases. JNJ0966 is a selective inhibitor of MMP-9 zymogen (IC50 = 440nM) that inhibits subsequent generation of the catalytically active enzyme. It showed no effect on the catalytic activity of MMP-1, MMP-2, MMP-3, MMP-9, or MMP-14, and did not inhibit the activation of MMP-2 zymogen. The addition of JNJ0966 (10μM) resulted in a significant reduction in fully processed MMP-9. The administration of JNJ0966 at 10 and 30mg/kg via oral gavage reduced motor deficits in a mouse model of experimental autoimmune encephalomyelitis (EAE). JNJ0966 also partitioned into the brain of EAE mice with brain/plasma ratios of 6.2 for the 10mg/kg dose and 4.7 for the 30mg/kg dose[1].
作用机制
JNJ0966 interacts with a structural pocket in proximity to the MMP-9 zymogen cleavage site near Arg-106[1].
JNJ0966 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Rat lens epithelial cells (LECs)
20 µM
48 hours
To validate the efficacy of JNJ0966 in inhibiting MMP9 and preventing TGF-β-induced epithelial-mesenchymal transition
Int J Mol Sci. 2021 Nov 5;22(21):11988.
HT1080 cells
1.0 μM
24 hours
To evaluate the effect of JNJ0966 on HT1080 cell invasion through a Matrigel extracellular matrix layer, results showed JNJ0966 significantly inhibited cell invasion
J Biol Chem. 2017 Oct 27;292(43):17963-17974.
JNJ0966 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Experimental autoimmune encephalomyelitis (EAE) model
Oral gavage
10 mg/kg and 30 mg/kg
Twice daily until day 17 of the study
To evaluate the therapeutic effect of JNJ0966 in the EAE model, results showed JNJ0966 significantly reduced disease severity
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