SR-31747
目录号 : GC31805
SR-31747 是一种具有免疫抑制和抗炎特性的 sigma 配体。
Cas No.:132173-06-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Animal experiment: |
IL-1, IL-6 and TNF-a are induced by i.p. injection of LPS into BALBIc mice. SR 31747 or reference substances are administered i.p. at the indicated doses together with LPS (0.5 mg/kg). Control animals are treated with LPS and vehicle. Blood samples are collected from the retro-orbital sinus 1 hr or 4 hr after LPS injection for the determination of TNF-α, IL-1 and IL-6. Plasma is prepared and stored frozen until experiments. The IL-1 plasma level is determined by a competitive radioreceptor assay with the use of the murine NOBEL4 cell line and [125I]-IL-1. The IL-6 assay is conducted with the B9 murine IL-6-dependent cell line. The TNF-a plasma level is evaluated by the cytolytic assay with the dactinomycin-treated LM6 cell line, derived from the murine fibroblastic L929 cell line. Each determination is performed on a pool of three different plasma samples. None of the molecules administered affect these assays even at the highest dose (10-5 M), which thereby rules out the possibility of any direct effect caused by the presence ofdrugs in treated-animal sera. In the various tests, one unit is defined as the amount of cytokines able to induce 50% of the maximal effect. |
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References: [1]. Derocq JM, et al. In vivo inhibition of endotoxin-induced pro-inflammatory cytokines production by the sigma ligand SR 31747. J Pharmacol Exp Ther. 1995 Jan;272(1):224-30. |
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SR-31747 is a new sigma ligand with immunosuppressive properties.
SR-31747 is capable of inhibiting T-cell proliferation when added as late as 24 h after activation. SR-31747 arrests proliferation in yeast cells in a dose-dependent manner[2].
SR 31747 dramatically blocks lipopolysaccharide-induced production of interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha in a dose-dependent manner (ED50 2 mg/kg)[1].
[1]. Derocq JM, et al. In vivo inhibition of endotoxin-induced pro-inflammatory cytokines production by the sigma ligand SR 31747. J Pharmacol Exp Ther. 1995 Jan;272(1):224-30. [2]. Silve S, et al. The immunosuppressant SR 31747 blocks cell proliferation by inhibiting a steroid isomerase in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Jun;16(6):2719-27.
| Cas No. | 132173-06-9 | SDF | |
| Canonical SMILES | CCN(C/C=C\C1=CC=C(C2CCCCC2)C(Cl)=C1)C3CCCCC3 | ||
| 分子式 | C23H34ClN | 分子量 | 359.98 |
| 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 | 2.7779 mL | 13.8897 mL | 27.7793 mL |
| 5 mM | 0.5556 mL | 2.7779 mL | 5.5559 mL |
| 10 mM | 0.2778 mL | 1.389 mL | 2.7779 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。
The immunosuppressant SR 31747 blocks cell proliferation by inhibiting a steroid isomerase in Saccharomyces cerevisiae
SR 31747 is a novel immunosuppressant agent that arrests cell proliferation in the yeast Saccharomyces cerevisiae, SR 31747-treated cells accumulate the same aberrant sterols as those found in a mutant impaired in delta 8- delta 7-sterol isomerase. Sterol isomerase activity is also inhibited by SR 31747 in in vitro assays. Overexpression of the sterol isomerase-encoding gene, ERG2, confers enhanced SR resistance. Cells growing anaerobically on ergosterol-containing medium are not sensitive to SR. Disruption of the sterol isomerase-encoding gene is lethal in cells growing in the absence of exogenous ergosterol, except in SR-resistant mutants lacking either the SUR4 or the FEN1 gene product. The results suggest that sterol isomerase is the target of SR 31747 and that both the SUR4 and FEN1 gene products are required to mediate the proliferation arrest induced by ergosterol depletion.
Immunopharmacological profile of SR 31747: in vitro and in vivo studies on humoral and cellular responses
In our preceding paper, we demonstrated that both human and rat lymphocytes possess saturable high-affinity binding sites for the new sigma ligand SR 31747. Here we investigate the potential activity of this ligand on immune responses. In vitro, our study shows that SR 31747 exerts a concentration- and time-dependent inhibition of proliferative response to mitogens on mouse and human lymphocytes without affecting cell viability. This suppressive effect elicited by SR 31747 occurs over a concentration range which correlates with the pharmacological profile of the molecule in binding assays, strongly suggesting that SR 31747 acts through a receptor-mediated process. We showed that the SR 31747 effect, which was observed on purified T lymphocytes, affects a late event in the activation process which occurs after the G1 during the S phase of the cell cycle. Interestingly, no anti-proliferative effect was observed in a variety of tumor cell lines, supporting a specific effect limited to normal immune cells. In vivo, in mice, treatment with SR 31747 prevented both graft-versus-host disease and delayed-type hypersensitivity granuloma formation, while antibody response to sheep red blood cells was not affected. These results strongly suggest that the sigma-related receptor recognized by SR 31747 is very likely coupled to a biological function of lymphocytes.
In vivo inhibition of endotoxin-induced pro-inflammatory cytokines production by the sigma ligand SR 31747
In previous studies, the authors demonstrated that the new sigma ligand, cis-N-cyclohexyl-N-ethyl-3-(3-chloro-4-cyclohexyl-phenyl) propen-2-ylamine hydrochloride (SR 31747), elicited a suppressive effect on immune responses through the sigma receptor expressed on lymphocytes. Here the effect of SR 31747 on the proinflammatory cytokine production by endotoxin-activated macrophages is examined. In vivo, SR 31747 dramatically blocked lipopolysaccharide-induced production of interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha in a dose-dependent manner (ED50, 2 mg/kg). Whereas SR 31747 suppression was not observed in vitro on lipopolysaccharide-induced IL-6 by macrophages, sera from SR 31747-treated animals displayed a strong inhibitory activity. It was shown that this effect could be completely reversed by the steroid receptor antagonist, mifepristone, which suggests that SR 31747 probably abrogated monokine production through an indirect mechanism that involves endogenous corticosteroids. This conclusion was supported by in vivo experiments that showed that 1) ablation of corticosteroids by use of mifepristone or adrenalectomy suppressed the effect of SR 31747 and 2) administration of SR 31747 induced an enhancement of the corticosterone level. It was also shown that this molecule improved the survival of animals with endotoxinic shock as a result of monokine inhibition. The combination of immunosuppression, previously described, along with anti-inflammatory properties makes SR 31747 a novel attractive molecule for therapeutic applications such as autoimmune diseases in which both immune and inflammatory disorders are involved.
In vivo effects of a new immunosuppressive sigma ligand, SR 31747, on mouse thymus
SR 31747 is a new sigma ligand which has immunosuppressive properties. The immunopharmacology of SR 31747 was investigated in vivo by studying its effects on the thymuses of C3H mice. The action of SR 31747 was compared with the reference drugs cyclosporin-A and dexamethasone on the basis of several parameters which were: the thymus weight; the number of thymocytes per organ; the percentages of mature CD4+ or CD8+ thymocytes and of immature CD4+ CD8+ thymocytes. SR 31747 slightly but significantly decreased the thymus weight at the dose of 50 mg/kg whereas the number of thymocytes per organ was significantly decreased from 6.25 mg/kg to the 50 mg/kg dose. It had rather no effect on the percentages of immature and mature subsets. These data led to the conclusion that the effects of SR 31747 on the thymuses of C3H mice were close to those obtained with cyclosporin-A and different from those obtained with dexamethasone.
The sigma ligand SR 31747 prevents the development of acute graft-versus-host disease in mice by blocking IFN-gamma and GM-CSF mRNA expression
SR 31747 is a sigma ligand which prevents the development of acute graft-versus-host reaction (GvHR) in hybrid B6D2F1 mice injected with C57BL/6 parental spleen cells. In the present study, we showed that this drug dramatically impaired the GvHR-associated increase in the numbers of both B-lymphocytes and polymorphonuclear cells (PMNs) in the spleen. Because SR 31747 blocked the GvHR-induced expression of both interleukin-2 and transferrin receptors on T-lymphocytes, it is very likely that this molecule prevented the disease through an inhibition of T-lymphocyte activation. Cytokine messenger RNA analyses on spleen cells revealed that SR 31747 blocked IFN-gamma and GM-CSF but not IL-4 transcription. These effects, which are different from those observed with either cyclosporin-A or dexamethasone, strongly suggest that SR 31747 preferentially inhibits the Th1 lymphocyte subset.