Bindarit
(Synonyms: 宾达利; AF2838) 目录号 : GC13335
Bindarit (2-methyl-2--1H-indazol-3yl) methoxy] propanoic acid) 是一种小分子，能够预防慢性炎症，从而降低炎症的细胞毒性作用炎症以及抑制 C-C 趋化因子的合成，包括 CCL2、CCL7 和 CCL8。
Cas No.:130641-38-2
Sample solution is provided at 25 µL, 10mM.
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Bindarit (2-methyl-2-[(1-[phenylmethyl]-1H-indazol-3yl) methoxy] propanoic acid) is a small molecule that is able to prevent the chronicity of inflammation and thus decrease the cytotoxic effects of inflammation as well as inhibit the synthesis of C–C chemokines including CCL2, CCL7, and CCL8. Treatment of Bindarit has been shown to lead to a dramatic reduction of urinary CCL2 and albumin excretion.[1]
In vitro study indicated that Bindarit selectively inhibited the production of the monocyte chemotactic protein subfamily of CC inflammatory chemokines (MCP-1/CCL2) at the transcriptional level. Other in vitro research also showed that Bindarit exerted a concentration-related neuroprotective activity against both Aβ25-35 and Aβ1-42 toxicity. Specifically, in cultures of mixed cortical neural cells, Bindarit reduced Aβ-related neurotoxicity in a dose-dependent manner. This effect correlated with CCL2 suppression at both mRNA and protein level.[2]
In vivo study demonstrated that Bindarit limited MCP-1/CCL2 upregulation in the kidney of PCK rats and that inhibition of the chemotactic signal translated in a reduced accumulation of inflammatory cells in the kidney. In vitro studies in murine podocytes exposed to albumin overload were instrumental to establish that amelioration of podocyte structure and antiproteinuric effect by Bindarit in PCK rats could be ascribed to drug’s ability of inhibiting podocyte MCP-1/ CCL2 production.[3]
References:
[1]. Shen Z, et al. Inhibition of CCL2 by Bindarit alleviates diabetes-associated periodontitis by suppressing inflammatory monocyte infiltration and altering macrophage properties. Cell Mol Immunol. 2021 Sep;18(9):2224-2235.
[2]. Severini C, et al. Bindarit, inhibitor of CCL2 synthesis, protects neurons against amyloid-β-induced toxicity. J Alzheimers Dis. 2014;38(2):281-93.
[3]. Zoja C, et al. Effects of MCP-1 inhibition by Bindarit therapy in a rat model of polycystic kidney disease. Nephron. 2015;129(1):52-61.
| Cell experiment [1]: | |
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Cell lines |
M2 macrophage |
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Preparation Method |
Macrophages (2 × 105) were sorted out from the peripheral blood of bone-cancer mice and treated with different concentrations of bindarit after IL-4 stimulation. |
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Reaction Conditions |
Treat macrophages with 0, 200, and 400 μM bindarit at 0, 2, and 6h after IL-4 stimulation. |
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Applications |
Bindarit significantly inhibited M2 macrophage polarization in vitro. Treatment of bindarit significantly decreased the level of Arg1 mRNA and functioned in a dose-dependent manner. mRNA levels of other M2 macrophage polarization markers Ym1, Mrc1, and Fizz1 were also down-regulated after bindarit treatment. Bindarit also inhibits phosphorylation of both IκBα and p65. |
| Animal experiment [1]: | |
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Animal models |
Adult male athymic nude mice, 7–8 weeks old, weighing 25–30 g |
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Preparation Method |
Mice received an intraperitoneal inoculation of breast sarcocarcinoma Walker 256 cells. Bone cancer was then established by inoculating Walker 256 cells (2 × 105 cells, 10 μL) into the intramedullary space of the mouse femur. Control mice (n = 20) were injected with heat-killed cancer cells. |
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Dosage form |
100 mg/kg |
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Applications |
Bindarit exhibited protective effect against bone-cancer-induced pain and inflammation. Treatment of bindarit also significantly improved the performance of the mice in spontaneous nocifensive behavior test and in mechanical hyperalgesia test, suggesting that treatment of bindarit significantly relieves the pain caused by bone cancer. Bindarit also reduced monocyte mobilization in peripheral blood. |
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References: [1]. Liu S, et al. Bindarit Attenuates Pain and Cancer-Related Inflammation by Influencing Myeloid Cells in a Model of Bone Cancer. Arch Immunol Ther Exp (Warsz). 2018 Jun;66(3):221-229. |
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| Cas No. | 130641-38-2 | SDF | |
| 别名 | 宾达利; AF2838 | ||
| 化学名 | 2-[(1-benzylindazol-3-yl)methoxy]-2-methylpropanoic acid | ||
| Canonical SMILES | CC(C)(C(=O)O)OCC1=NN(C2=CC=CC=C21)CC3=CC=CC=C3 | ||
| 分子式 | C19H20N2O3 | 分子量 | 324.37 |
| 溶解度 | ≥ 16.2mg/mL 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 | 3.0829 mL | 15.4145 mL | 30.829 mL |
| 5 mM | 0.6166 mL | 3.0829 mL | 6.1658 mL |
| 10 mM | 0.3083 mL | 1.5414 mL | 3.0829 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet