MMP-8 Inhibitor I is a potent matrix metalloproteinase-8 (MMP-8) inhibitor with low oral bioavailability[1]. MMP-8 has emerged as a key tumor-suppressive enzyme[2]. The absence of MMP-8 has multiple consequences for angiogenesis, innate immune responses and metastasis that conspire to promote tumor growth and malignancy[3].
MMP-8 Inhibitor I (10μM, 48h) effectively prevented the degradation of tight junction proteins (ZO-1, Occludin, Claudin-5) caused by the virus supernatant in bEnd.3 cells[4]. MMP-8 Inhibitor I (5nM, 24h) significantly downregulated Col1A1 and α-SMA expression in LX-2 cells[5].
MMP-8 Inhibitor I (1mg/kg, days 2 and 4 post-infection, i.p.) effectively inhibited the degradation of ZO-1, Occludin, and Claudin-5 in the brains of mice in the lab-attenuated RABV infection model[4]. MMP-8 Inhibitor I (5mg/kg/day, 28 days, i.p.) significantly reduced MMP-8 activity in aortic tissue in a thoracic aortic dissection (TAD) mouse model[6].
References:
[1] Matter H, Schudok M, Schwab W, et al. Tetrahydroisoquinoline-3-carboxylate based matrix-metalloproteinase inhibitors: design, synthesis and structure–activity relationship[J]. Bioorganic & medicinal chemistry, 2002, 10(11): 3529-3544.
[2] Dufour A, Overall C M. Missing the target: matrix metalloproteinase antitargets in inflammation and cancer[J]. Trends in pharmacological sciences, 2013, 34(4): 233-242.
[3] Decock J, Hendrickx W, Thirkettle S, et al. Pleiotropic functions of the tumor-and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice[J]. Breast Cancer Research, 2015, 17(1): 38.
[4] Fang A, Yuan Y, Huang F, et al. Lab-attenuated rabies virus facilitates opening of the blood-brain barrier by inducing matrix metallopeptidase 8[J]. Journal of virology, 2022, 96(17): e01050-22.
[5] Naim A, Baig M S. Matrix metalloproteinase-8 (MMP-8) regulates the activation of hepatic stellate cells (HSCs) through the ERK-mediated pathway[J]. Molecular and Cellular Biochemistry, 2020, 467(1): 107-116.
[6] Zhang C, Niu K, Ren M, et al. Targeted inhibition of matrix metalloproteinase-8 prevents aortic dissection in a murine model[J]. Cells, 2022, 11(20): 3218.
MMP-8 Inhibitor I是一种强效的基质金属蛋白酶-8（MMP-8）抑制剂，但口服生物利用度较低[1]。MMP-8已被证实是一种重要的肿瘤抑制酶[2]。MMP-8的缺失会对血管生成、先天免疫反应和转移产生多种影响，这些影响共同促进肿瘤生长和恶性转化[3]。
MMP-8 Inhibitor I（10μM，48h）能有效抑制病毒上清液在bEnd.3细胞中引起的紧密连接蛋白（ZO-1、Occludin、Claudin-5）的降解[4]。MMP-8 Inhibitor I（5nM，24h）能显著下调LX-2细胞中Col1A1和α-SMA的表达[5]。
MMP-8 Inhibitor I（1mg/kg，感染后第2天和第4天，腹腔注射）可有效抑制实验室减毒RABV感染模型小鼠脑中ZO-1、Occludin和Claudin-5的降解[4]。MMP-8 Inhibitor I（5mg/kg/天，28天，腹腔注射）可显著降低胸主动脉夹层（TAD）小鼠模型中主动脉组织内的MMP-8活性[6]。