SB 290157 (trifluoroacetate salt)
目录号 : GC11800
SB 290157（三氟乙酸盐）用作选择性非肽类 C3aR 拮抗剂。
Cas No.:1140525-25-2
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Vascular smooth muscle cells (VSMCs) from SHR and WKY rats |
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Preparation Method |
VSMCs were inoculated and grown into DMEM containing 5% calf serum in the absence or presence of 0.1µmol/l SB 290157 (trifluoroacetate salt) in 24-well culture dishes at a density of 105 cells/cm3. Cells were trypsinized with 0.05% trypsin at 24, 48, and 72 h after inoculation, and cell numbers were counted in a Coulter counter. |
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Reaction Conditions |
0.1µmol/l for 24, 28, 72 hours |
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Applications |
SB290157 significantly inhibited the increase in the number of VSMCs in SHR rats, whereas SB 290157 (trifluoroacetate salt) did not affect the increase in the number of cells in WKY rats. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6JNarl (B6) mice |
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Preparation Method |
Stock solution of SB 290157 was prepared by dissolving the compound in a minimal volume of sterile DMSO (100 mg.ml-1). SB 290157 (trifluoroacetate salt) was further diluted with 1× sterile PBS for injection to a final dose of 20 mg.kg-1 body weight in 100 µl volume. In the photothrombotic stroke model, SB 290157 (trifluoroacetate salt) or vehicle was injected intraperitoneally 1 hr after stroke while in the embolic clot middle cerebral artery occlusion model, it was intravenously injected 2 hr post-stroke. |
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Dosage form |
Intraperitoneal or intravenous injection, 20 mg.kg-1 |
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Applications |
SB 290157 (trifluoroacetate salt) treatment 1 hr after photothrombotic stroke significantly improved neurofunctional outcome assessed by the adhesive tape removal and corner turn tests. SB 290157 (trifluoroacetate salt) significantly reduced the infarct volume relative to vehicle-treated animals at 48 hr post-photothrombotic. |
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References: [1]: Han Y, Fukuda N, Ueno T, et al. Role of complement 3a in the synthetic phenotype and angiotensin II-production in vascular smooth muscle cells from spontaneously hypertensive rats[J]. American journal of hypertension, 2012, 25(3): 284-289. | |
SB 290157 (trifluoroacetate salt) is used as a selective nonpeptide C3aR antagonist. SB 290157 was a selective antagonist for rat basophilic leukemia cells expressing the human C3aR (IC50 of 200 nM). Antagonism by SB 290157 was not only limited to the human C3aR (IC50 of 12 nM), it also inhibited C3a-induced Ca2+ mobilization of cells expressing the mouse and guinea-pig C3aR (IC50 of 7 and 30 nM, respectively). [1].
SB 290157 (trifluoroacetate salt) (0.1 μM) significantly increased the abundance of SM22α mRNA and decreased the abundance of osteopontin mRNA in VSMCs from SHR rats, but these did not occur in cells from WKY rats [2]. C3a overexpression markedly altered the distribution of vinculin in human podocyte line cells, C3aR inhibition with 1 μM SB 290157 blocked this alteration [3]. SB 290157(0.1-10μM) inhibited C3aR internalization induced by 10 nM C3a in a concentration-dependent manner. In the presence of >1 μM concentrations of SB 290157 the internalization of the C3aR induced by C3a was reduced by ～50% [4].
SB 290157 (trifluoroacetate salt) (1 mg/kg) treatment reduced microglial activation and cognitive deficits in lipopolysaccharide (LPS) induced mice. SB 290157 (trifluoroacetate salt) attenuated LPS-induced hippocampal neuroinflammation and inhibitory synapse related protein loss, contributing to improved cognitive function of mice [5]. SB 290157 (trifluoroacetate salt) was involved in the suppression of anti-OVA pAb-induced arthritis, injection of SB 290157 at concentrations of 30 mg/kg, SB 290157 was able to reduce joint swelling at 3 h, and inhibit about 50% inhibition of joint swelling [6].
References:
[1]. Ames R S, Lee D, Foley J J, et al. Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a receptor that demonstrates antiinflammatory activity in animal models[J]. The Journal of Immunology, 2001, 166(10): 6341-6348.
[2]. Han Y, Fukuda N, Ueno T, et al. Role of complement 3a in the synthetic phenotype and angiotensin II-production in vascular smooth muscle cells from spontaneously hypertensive rats[J]. American journal of hypertension, 2012, 25(3): 284-289.
[3]. Zheng J M, Wang S S, Tian X, et al. Sustained activation of C3aR in a human podocyte line impairs the morphological maturation of the cells[J]. Molecular medicine reports, 2020, 22(6): 5326-5338.
[4]. Ames R S, Lee D, Foley J J, et al. Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a receptor that demonstrates antiinflammatory activity in animal models[J]. The Journal of Immunology, 2001, 166(10): 6341-6348.
[5]. Li S, Li B, Zhang L, et al. A complement-microglial axis driving inhibitory synapse related protein loss might contribute to systemic inflammation-induced cognitive impairment[J]. International Immunopharmacology, 2020, 87: 106814.
[6]. Hutamekalin P, Takeda K, Tani M, et al. Effect of the C3a-receptor antagonist SB 290157 on anti-OVA polyclonal antibody-induced arthritis[J]. Journal of pharmacological sciences, 2010, 112(1): 56-63.
SB 290157（三氟乙酸盐）用作选择性非肽类 C3aR 拮抗剂。 SB 290157 是表达人 C3aR 的大鼠嗜碱性白血病细胞的选择性拮抗剂（IC50 为 200 nM）。 SB 290157 的拮抗作用不仅限于人 C3aR（IC50 为 12 nM）,它还抑制 C3a 诱导的表达小鼠和豚鼠 C3aR 的细胞的 Ca2+ 动员（IC50 分别为 7 和 30 nM）。 [1].
SB 290157（三氟乙酸盐）(0.1 μM) 可显着增加 SHR 大鼠 VSMC 中 SM22α mRNA 的丰度并降低骨桥蛋白 mRNA 的丰度,但这些并未发生在 WKY 大鼠的细胞中 [2]。 C3a 过表达显着改变了人足细胞系细胞中纽蛋白的分布,用 1 μM SB 290157 抑制 C3aR 可阻断这种改变[3]。 SB 290157(0.1-10μM) 以浓度依赖性方式抑制由 10 nM C3a 诱导的 C3aR 内化。在 >1 μM 浓度的 SB 290157 存在下,C3a 诱导的 C3aR 内化减少了 ~ 50% [4]。
SB 290157（三氟乙酸盐）(1 mg/kg) 处理可减少脂多糖 (LPS) 诱导的小鼠的小胶质细胞活化和认知缺陷。 SB 290157（三氟乙酸盐）可减轻 LPS 诱导的海马神经炎症和抑制性突触相关蛋白丢失,有助于改善小鼠的认知功能[5]。 SB 290157（三氟乙酸盐）参与抗OVA pAb诱导的关节炎的抑制,注射浓度为30 mg/kg的SB 290157,SB 290157能够在3 h时减轻关节肿胀,并抑制约50%的抑制作用关节肿胀 [6].
| Cas No. | 1140525-25-2 | SDF | |
| 化学名 | N2-[2-(2,2-diphenylethoxy)acetyl]-L-arginine, 2,2,2-trifluoroacetate | ||
| Canonical SMILES | O=C(N[C@H](C(O)=O)CCCNC(N)=N)COCC(C1=CC=CC=C1)C2=CC=CC=C2.FC(F)(C(O)=O)F | ||
| 分子式 | C22H28N4O4 • CF3COOH | 分子量 | 526.5 |
| 溶解度 | ≤30mg/ml in ethanol;20mg/ml in DMSO;25mg/ml in dimethyl formamide | 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 | 1.8993 mL | 9.4967 mL | 18.9934 mL |
| 5 mM | 0.3799 mL | 1.8993 mL | 3.7987 mL |
| 10 mM | 0.1899 mL | 0.9497 mL | 1.8993 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 | ||||||||||
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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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C3/C3aR inhibition alleviates GMH-IVH-induced hydrocephalus by preventing microglia-astrocyte interactions in neonatal rats
Neuropharmacology.2022 Mar 1;205:108927PMID: 34921829 DOI: 10.1016/j.neuropharm.2021.108927
Activation of microglia and astrocytes following germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) plays a detrimental role in posthemorrhagic hydrocephalus (PHH). It is still unclear whether or how an interaction occurs between microglia and astrocytes in PHH. Here, we investigated the role of the C3/C3aR pathway in microglia and astrocyte interactions and whether C3/C3aR-targeted inhibition could alleviate PHH following GMH-IVH. A total of 152 Sprague-Dawley rats at postnatal day seven (P7) were enrolled in the study, and collagenase VII was used to induce GMH-IVH. Minocycline (45 mg/kg) was administered to inhibit microglial activation. Complement C3a peptide and C3aR antagonist (SB 290157, 10 mg/kg) were used to regulate the C3/C3aR pathway. As a result, the data demonstrated that periventricular C3aR+/Iba-1+ microglia and C3+/GFAP+ astrocytes were significantly increased in GMH-IVH pups at 28 days after surgery. Intranasal C3a peptide upregulated C3aR expression in microglia. Inhibition of microglia by minocycline decreased both C3+/GFAP+ astrocytes and the colocalization volume of Iba-1 and GFAP. In addition, intraperitoneally injected C3aRA alleviated the periventricular colocalization volume of microglia and astrocytes. Compared with vehicle-treated pups, the protein level of IL-1β, IL-6 and TNF-α in cerebral spinal fluid and brain tissue at 28 days following GMH-IVH were reduced in C3aRA-treated pups. Moreover, hydrocephalus was alleviated, and long-term cognitive ability were improved in the C3aRA-treated group. Our data presented simultaneous periventricular astrogliosis and microgliosis of pups following GMH-IVH and proved their potential interaction through the C3/C3aR pathway, indicating C3aRA as a potential pharmacological treatment of PHH in neonates.
The C3a receptor antagonist SB 290157 has agonist activity
Immunol Lett 2005 Sep 15;100(2):139-45. PMID: 16154494DOI: 10.1016/j.imlet.2005.03.003
The anaphylatoxin C3a is an important immune regulator with a number of distinct functions in both innate and adaptive immunity. Many of these roles have been ascribed to C3a based on studies in mice genetically modified to lack its precursor, C3, or its receptor, C3aR. However, other presumed functions of C3a are based on results obtained with a recently described small molecule ligand of C3aR, SB 290157. Although this compound was originally described as an antagonist and appears to act as such in some systems, it has recently been shown to have effects that cannot be explained by simple antagonism of C3aR. In the current study, SB 290157 is shown to have full agonist activity on C3aR in a variety of cell systems, including a calcium mobilization assay in transfected RBL cells, a beta-lactamase assay in CHO-NFAT-bla-Galpha(16) cells and an enzyme-release assay in differentiated U-937 cells. On the other hand, the compound lacks agonist activity in guinea pig platelets, cells known to express C3aR at very low levels. SB 290157 agonism of C3aR is consistent with recent discrepant data obtained using this molecule. These results caution against attributing novel roles to C3a based on data obtained with SB 290157 and highlight a continuing need for the identification of true small molecule C3aR antagonists.
Effect of the C3a-receptor antagonist SB 290157 on anti-OVA polyclonal antibody-induced arthritis
J Pharmacol Sci 2010;112(1):56-63.PMID: 20051658DOI: 10.1254/jphs.09180fp
It was investigated whether the C3a-receptor antagonist (C3aRA) SB 290157 was involved in the suppression of anti-OVA pAb-induced arthritis because it is well known that anaphylatoxin C3a plays a crucial role in the development of an effective inflammatory response during complement activation. Anti-OVA pAb-induced arthritis was induced in DBA/1J mice by administration of anti-OVA pAb 0.5 h prior to intra-articular (i.a.) injection of OVA (0 h). Two peaks of joint swelling were observed at 0.5 and 3 h. The role of C3aRA in arthritis was investigated by injection of SB 290157 at concentrations of 10 and 30 mg/kg at 0 and 2 h. The antagonist was able to reduce joint swelling only at 3 h, and about 50% inhibition of joint swelling was observed with the concentration of 30 mg/kg. The C3 level was significantly decreased at 3 h compared with naïve mice showing complement consumption. Furthermore, the C3 activation was observed and increased corresponding to the graded concentration of anti-OVA pAb. The results also revealed that the C3aRA was able to reduce the expression of IL-1beta in synovial tissue. Taken together, the results suggested that C3aRA may be effective in the inhibition of arthritis.