Ro 31-9790 (GI4747)
(Synonyms: GI4747) 目录号 : GC33881
Ro 31-9790 (GI4747) 是一种合成金属蛋白酶 (MMP) 抑制剂。
Cas No.:145337-55-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | For mouse and human lymphocytes and Jurkat T cells, 100% inhibition is set as the percentage of cells positive for L-selectin in an untreated sample (after flow cytometric analysis) or the concentration of soluble L-selectin in the supernatant of an untreated cell sample (after ELISA); 0% inhibition is set at the appropriate value for a PMA-treated sample. For results from human monocytes, a different calculation is needed to allow direct comparison of L-selectin and TNF-α shedding. Therefore, in this case 100% inhibition is set as the percentage of cells positive for L-selectin in the presence of PMA+50 μM Ro 31-9790 or the percentage of cells positive for cell surface TNF-α in the presence of LPS+50 μM Ro 31-9790 (doses of Ro 31-9790 which gave maximal inhibition); 0% inhibition is set as the percentage of cells positive for L-selectin or TNF-α in the presence of PMA or LPS, respectively. Intermediate percent inhibition is calculated. The IC50 value for inhibitor in each system is defined as the concentration of inhibitor which gave 50% inhibition, where 100% inhibition is set as the percentage of cells positive for L-selectin or cell surface TNF-α in the presence of Phorbol myristate acetate (PMA)+50 μM Ro 31-9790 or Lipopolysaccharide (LPS)+50 μM Ro 31-9790, respectively (doses of Ro 31-9790 which gave maximal inhibition) and 0% inhibition is set as the percentage of cells positive for L-selectin or TNF-α in the presence of PMA or LPS alone, respectively[1]. |
References: [1]. Borland G, et al. Tissue inhibitor of metalloproteinases-3 inhibits shedding of L-selectin from leukocytes. J Biol Chem. 1999 Jan 29;274(5):2810-5. | |
Ro 31-9790 is a synthetic metalloproteinase (MMP) inhibitor.
Ro 31-9790 inhibits L-selectin shedding from mouse and human lymphocytes, Jurkat T cells, and human monocytes with an IC50 of 0.3-0.4 μM on these cell types. The IC50 values obtained for Ro 31-9790 are 4.82 ± 0.75 μM, 1.16 ± 0.27 μM, 0.70 ± 0.06 μM, 4.47± 1.27 μM and 0.38 ± 0.05 μM for mouse lymphocyte L-selectin shedding, Jurkat L-selectin shedding, human lymphocyte L-selectin shedding, human monocyte L-selectin shedding and human monocyte TNF-α shedding[1].
[1]. Borland G, et al. Tissue inhibitor of metalloproteinases-3 inhibits shedding of L-selectin from leukocytes. J Biol Chem. 1999 Jan 29;274(5):2810-5.
| Cas No. | 145337-55-9 | SDF | |
| 别名 | GI4747 | ||
| Canonical SMILES | O=C(N[C@H](C(NC)=O)C(C)(C)C)[C@H](CC(C)C)CC(NO)=O | ||
| 分子式 | C15H29N3O4 | 分子量 | 315.41 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1705 mL | 15.8524 mL | 31.7048 mL |
| 5 mM | 0.6341 mL | 3.1705 mL | 6.341 mL |
| 10 mM | 0.317 mL | 1.5852 mL | 3.1705 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Tissue inhibitor of metalloproteinases-3 inhibits shedding of L-selectin from leukocytes
J Biol Chem 1999 Jan 29;274(5):2810-5.PMID:9915814DOI:10.1074/jbc.274.5.2810.
Although the enzyme or enzymes mediating shedding of L-selectin have not yet been identified, this activity can be blocked by synthetic hydroxamic acid-based inhibitors of metalloproteinases such as Ro 31-9790. However, the endogenous matrix metalloproteinase inhibitor tissue inhibitor of metalloproteinases (TIMP)-1 does not block L-selectin shedding. Here, we report that TIMP-3, but not TIMP-2, inhibits L-selectin shedding from mouse and human lymphocytes, Jurkat T cells, and human monocytes. TIMP-3 has an IC50 of 0.3-0.4 microM on these cell types compared with 0.7-4.8 microM for Ro 31-9790. A metalloproteinase (tumor necrosis factor-alpha (TNF-alpha)-converting enzyme; ADAM17) has recently been identified which cleaves the pro-form of TNF-alpha to produce soluble cytokine. We compared inhibition of L-selectin shedding by TIMPs and Ro 31-9790 with inhibition of TNF-alpha shedding from human monocytes. TIMP-3 inhibited TNF-alpha shedding (IC50 of 0.1 microM), as did Ro 31-9790 (IC50 of 0.4 microM). TIMP-2 had a partial effect, and TIMP-1 did not inhibit. This study confirms that L-selectin sheddase is a metalloproteinase, but not a matrix metalloproteinase, and investigates the relationship between shedding of L-selectin and TNF-alpha.
Transendothelial migration of lymphocytes across high endothelial venules into lymph nodes is affected by metalloproteinases
Blood 2001 Aug 1;98(3):688-95.PMID:11468168DOI:10.1182/blood.v98.3.688.
The migration of lymphocytes from the bloodstream into lymph nodes (LNs) via high endothelial venules (HEVs) is a prerequisite for the detection of processed antigen on mature dendritic cells and the initiation of immune responses. The capture and arrest of lymphocytes from flowing blood is mediated by the multistep adhesion cascade, but the mechanisms that lymphocytes use to penetrate the endothelial lining and the basement membrane of HEVs are poorly understood. Matrix metalloproteinases (MMPs) control the metastatic spread of tumor cells by regulating the penetration blood vessel basement membranes. In this study, synthetic and natural inhibitors were used to determine the role of MMPs and MMP-related enzymes in regulating lymphocyte extravasation in mice. Mice were treated systemically with the hydroxamate-based MMP inhibitor Ro 31-9790 and plasma monitored for effective levels of Ro 31-9790, which block shedding of L-selectin. The total numbers of lymphocytes recruited into LNs were not altered, but L-selectin levels were higher in mice treated with Ro 31-9790. A reduced number of lymphocytes completed diapedesis and there was an increase in the number of lymphocytes in the endothelial cell lining, rather than the lumen or the basement membrane of HEVs. Lymphocyte migration and L-selectin expression in the spleen were not altered by Ro 31-9790 treatment. Two MMP inhibitors, TIMP1 and Ro 32-1541, did not block L-selectin shedding and had no effect on lymphocyte migration across HEVs. These results suggest that metalloproteinase activity is required for lymphocyte transmigration across HEVs into LNs and provide evidence for the concept that metalloproteinases are important players in some forms of transendothelial migration. (Blood. 2001;98:688-695)
Metalloproteinase-mediated regulation of L-selectin levels on leucocytes
J Biol Chem 1996 May 17;271(20):11634-40.PMID:8662605DOI:10.1074/jbc.271.20.11634.
Leucocyte (L)-selectin can be proteolytically cleaved in the membrane proximal extracellular region to yield a soluble fragment that contains the functional lectin and epidermal growth factor domains. A variety of stimuli are known to stimulate L-selectin shedding including chemoattractants, phorbol esters, and L-selectin cross-linking; however, the enzymes that regulate L-selectin expression are not characterized. In this study we have used phorbol ester to stimulate endoproteolytic release of L-selectin and identified a major role for a cell surface metalloproteinase (L-selectin sheddase) in this process. The hydroxamic acid-based inhibitor of zinc-dependent matrix metalloproteinases Ro 31-9790 completely prevented shedding of cell surface L-selectin from leucocytes in mouse, rat, and man. L-selectin was susceptible to cleavage by known matrix metalloproteinases. Recombinant human fibroblast collagenase (MMP1) reduced the number of L-selectin-positive lymphocytes to a similar extent as phorbol ester activation, and stromelysin (MMP3) had a partial effect on L-selectin expression. Gelatinases A (MMP2) and B (MMP9) were without effect. Lymphocytes did not express fibroblast collagenase or stromelysin at the cell surface, and tissue inhibitor of metalloproteinases (TIMP) did not affect L-selectin levels. L-selectin sheddase was not detected in media harvested from phorbol ester-stimulated lymphocytes and was only able to cleave L-selectin in the cis but not the trans configuration. These results suggest that endoproteolytic release of L-selectin from the leucocyte surface is mediated by a metalloproteinase (L-selectin sheddase), which is distinguishable from known matrix metalloproteinases. Understanding the regulation of L-selectin sheddase will be critical for controlling leucocyte migration from the blood.
Chondrocytes and antirheumatic drugs
J Rheumatol Suppl 1995 Feb;43:152-4.PMID:7538587doi
Effects of antirheumatic drugs upon cartilage matrix metabolism have been studied in a variety of chondrocyte in vitro systems. When compared longterm in 60 experiments under standardized conditions, articular chondrocytes cultured in agarose exhibit variability in proteoglycan synthesis, and its suppression by interleukin 1 (IL-1), but a high reproducibility in the modulation of these effects by antirheumatic drugs. Pentosan polysulfate, tenidap, tiaprofenic acid, and Ro 31-9790 all compensated to a certain extent the IL-1 induced suppression of matrix synthesis in bovine chondrocytes, but only for tiaprofenic acid could this be confirmed using chondrocytes of human origin. Culture conditions as well as species differences should therefore be considered carefully when chondrocyte cultures are used as pharmacological models.
Hydrogen peroxide causes cardiac dysfunction independent from its effects on matrix metalloproteinase-2 activation
Can J Physiol Pharmacol 2007 Mar-Apr;85(3-4):341-8.PMID:17612643DOI:10.1139/y07-003.
Hydrogen peroxide (H2O2) causes cardiac dysfunction through multiple mechanisms. As oxidative stress can activate matrix metalloproteinases (MMPs) and, in particular, MMP-2 activity is associated with oxidative stress injury in the heart, we hypothesized that MMP-2 activation by H2O2 in isolated rat hearts contributes to cardiac dysfunction in this model. Isolated working rat hearts were perfused at 37 degrees C with a recirculating Krebs-Henseleit buffer+/-5 mmol/L pyruvate, known to protect hearts from oxidative stress. H2O2 (300 micromol/L) was added as a single bolus after 20 min of equilibration, and cardiac function was monitored for 60 min. MMPs activities in both the heart and perfusate samples were assessed by gelatin zymography. Tissue high energy phosphates were analysed by HPLC. The actions of 2 MMP inhibitors, doxycycline (75 micromol/L) or Ro 31-9790 (3 micromol/L), were also assessed. H2O2 at 300 micromol/L produced a rapid decline in cardiac mechanical function, which was maximal at 5 min. A peak in perfusate MMP-2 activity was also observed at 5 min. The deleterious effect of H2O2 on cardiac function was abolished by pyruvate but not by the MMPs inhibitors. This study suggests that in intact hearts, H2O2 induces contractile dysfunction independent of MMPs activation.