MMP-8 Inhibitor I
(Synonyms: Matrix Metalloproteinase-8 Inhibitor I) 目录号 : GC18616MMP-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。
Cas No.:236403-25-1
Sample solution is provided at 25 µL, 10mM.
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]。
| Cell experiment [1]: | |
Cell lines | Brain-derived endothelial cell line bEnd.3 |
Preparation Method | C57BL/6 mice (n = 3) were i.c. inoculated with 20 FFU of rRABV (recombinant rabies virus) or mock infected with DMEM at the same volume. At 6 d.p.i., mouse brains were harvested and used for further analysis. bEnd.3 cells were treated with supernatants in the presence of MMP-8 Inhibitor I (10μM) or DMSO for 48h and then harvested to measure the Occludin, Claudin-5, and ZO-1 levels by Western blotting and immunofluorescence. |
Reaction Conditions | 10μM, 48h |
Applications | MMP-8 Inhibitor I effectively prevented the degradation of tight junction proteins (ZO-1, Occludin, Claudin-5) caused by the virus supernatant in bEnd.3 cells. |
| Animal experiment [1]: | |
Animal models | Lab-attenuated RABV-infected mouse model |
Preparation Method | Two groups of C57BL/6 mice (n = 3) were i.c. inoculated with 20 FFU of CVS. One group of C57BL/6 mice (n = 3) were i.c. inoculated with the same volume of DMEM. MMP-8 Inhibitor I was dissolved in 1% DMSO in PBS to a final concentration of 0.01mg/mL. The CVS-infected mice received a 1-mg/kg (of body weight) dose of inhibitor or the same volume of a vehicle (1% DMSO in PBS) at 2 and 4 d.p.i. At 6 d.p.i., mice were injected intraperitoneally with 100μL of NaF (100mg/mL), and the BBB integrity was calculated based on NaF uptake in the brains. The infected mouse brains at 6 d.p.i. were collected, and the Occludin, Claudin-5, and ZO-1 expression levels were determined by Western blotting. |
Dosage form | 1mg/kg, days 2 and 4 post-infection, i.p. |
Applications | MMP-8 Inhibitor I effectively inhibited the degradation of ZO-1, Occludin, and Claudin-5 in the mouse brains. |
References: | |
| Cas No. | 236403-25-1 | SDF | |
| 别名 | Matrix Metalloproteinase-8 Inhibitor I | ||
| 化学名 | (3R)-1,2,3,4-tetrahydro-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl]-3-isoquinolinecarboxamide | ||
| Canonical SMILES | O=C(NO)[C@@H]1N(S(C2=CC=C(OC)C=C2)(=O)=O)CC3=CC=CC=C3C1 | ||
| 分子式 | C17H18N2O5S | 分子量 | 362.4 |
| 溶解度 | DMSO: 200 mg/ml | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7594 mL | 13.7969 mL | 27.5938 mL |
| 5 mM | 551.9 μL | 2.7594 mL | 5.5188 mL |
| 10 mM | 275.9 μL | 1.3797 mL | 2.7594 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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Quality Control & SDS
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- Purity: >98.00%
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