Heparastatin
(Synonyms: SF4) 目录号 : GC31531
An inhibitor of heparanase
Cas No.:153758-25-9
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: | Influence of a heparanase inhibitor on TGF-β3-induced EMT of NMuMG cells. NMuMG cells are cultured with 1 ng/mL TGF-β3 together with 10 or 100 μM Heparastatin (SF4) for 48 h[2]. |
References: [1]. Sue M, et al. An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouches. Int Immunopharmacol. 2016 Jun;35:15-21. | |
Heparastatin is an inhibitor of heparanase, an enzyme that cleaves heparan sulfate into glucuronic acid (GlcUA) and N-acetylglucosamine (GlcNAc).1 It inhibits heparanase in A375-M human melanoma cells expressing the recombinant human enzyme (IC50 = 10.55 ?M). Heparastatin also inhibits bovine liver β-glucuronidase and almond β-glucosidase (IC50s = 0.31 and 11 ?M, respectively). It reduces air pouch neutrophil and monocyte infiltration and levels of chemokine (C-C motif) ligand 2 (CCL2) in a mouse model of dorsal air pouch inflammation induced by carrageenan.2 Heparastatin (100 mg/kg once per day) inhibits metastasis by 57.1% in a murine Lewis lung carcinoma model.3
1.Nishimura, Y., Shitara, E., Adachi, H., et al.Flexible synthesis and biological activity of uronic acid-type gem-diamine 1-N-iminosugars: A new family of glycosidase inhibitorsJ. Org. Chem.65(1)2-11(2000) 2.Sue, M., Higashi, N., Shida, H., et al.An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouchesInt. Immunopharmacol.3515-21(2016) 3.Nishimura, Y., Satoh, T., Kondo, S., et al.Effect on spontaneous metastasis of mouse Lewis lung carcinoma by a trifluoroacetamide analogue of siastatin BJ. Antibiot. (Tokyo)47(7)840-842(1994)
| Cas No. | 153758-25-9 | SDF | |
| 别名 | SF4 | ||
| Canonical SMILES | O=C([C@H]1CN[C@H](NC(C(F)(F)F)=O)[C@@H](O)[C@H]1O)O | ||
| 分子式 | C8H11F3N2O5 | 分子量 | 272.18 |
| 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 | 3.674 mL | 18.3702 mL | 36.7404 mL |
| 5 mM | 0.7348 mL | 3.674 mL | 7.3481 mL |
| 10 mM | 0.3674 mL | 1.837 mL | 3.674 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouches
Local infiltration of inflammatory cells is regulated by a number of biological steps during which the cells likely penetrate through subendothelial basement membranes that contain heparan sulfate proteoglycans. In the present study, we examined whether administration of heparastatin (SF4), an iminosugar-based inhibitor of heparanase, could suppress local inflammation and degradation of heparan sulfate proteoglycans in basement membranes. In a carrageenan- or formyl peptide-induced dorsal air pouch inflammation model, the number of infiltrated neutrophils and monocytes was significantly lower in mice after topical administration of heparastatin (SF4). The concentration of chemokines MIP-2 and KC in pouch exudates of drug-treated mice was similar to control. In a zymosan-induced peritonitis model, the number of infiltrated cells was not altered in drug-treated mice. To further test how heparastatin (SF4) influences transmigration of inflammatory neutrophils, its suppressive effect on migration and matrix degradation was examined in vitro. In the presence of heparastatin (SF4), the number of neutrophils that infiltrated across a Matrigel-coated polycarbonate membrane was significantly lower, while the number of neutrophils passing through an uncoated membrane was not altered. Lysate of bone marrow-derived neutrophils released sulfate-radiolabeled macromolecules from basement membrane-like extracellular matrix, which was suppressed by heparastatin (SF4). Heparan sulfate degradation activity was almost completely abolished after incubation of lysate with protein G-conjugated anti-heparanase monoclonal antibody, strongly suggesting that the activity was due to heparanase-mediated degradation. Taken together, in a dorsal air pouch inflammation model heparastatin (SF4) potentially suppresses extravasation of inflammatory cells by impairing the degradation of basement membrane heparan sulfate.
Heparanase augments inflammatory chemokine production from colorectal carcinoma cell lines
To explore possible roles of heparanase in cancer-host crosstalk, we examined whether heparanase influences expression of inflammatory chemokines in colorectal cancer cells. Murine colorectal carcinoma cells incubated with heparanase upregulated MCP-1, KC, and RANTES genes and released MCP-1 and KC proteins. Heparanase-dependent production of IL-8 was detected in two human colorectal carcinoma cell lines. Addition of a heparanase inhibitor Heparastatin (SF4) did not influence MCP-1 production, while both latent and mature forms of heparanase augmented MCP-1 release, suggesting that heparanase catalytic activity was dispensable for MCP-1 production. In contrast, addition of heparin to the medium suppressed MCP-1 release in a dose-dependent manner. Similarly, targeted suppression of Ext1 by RNAi significantly suppressed cell surface expression of heparan sulfate and MCP-1 production in colon 26 cells. Taken together, it is concluded that colon 26 cells transduce the heparanase-mediated signal through heparan sulfate binding. We propose a novel function for heparanase independent of its endoglycosidase activity, namely as a stimulant for chemokine production.