SR9011
目录号 : GC17310
A REV-ERBα/β agonist
Cas No.:1379686-29-9
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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Cell experiment: |
MCF10A, MDA-MB-231, MCF-7, MDA-MB-361, SKBR3, BT474 cells are plated in 6-well plates one day before treatment. The MTT cell proliferation assays are performed. Briefly, 3×103 to 5 × 103 cells per well are plated in 96-well plates. Twenty-four hours later, cells are treated with SR9011 (0, 2, 4, 6, 8 and 10 μM) or DMSO. Seventy-two hours after treatment, the cells are labeled with 1.2 mM MTT and incubated for 4 hours. DMSO is then added and readings are taken on a plate reader at 540 nm[2]. |
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Animal experiment: |
Mice[1] For circadian gene expression experiments male C57BL6 mice (8-10 weeks of age) are either maintained on a L:D (12h:12h) cycle or on constant darkness. At circadian time (CT) 0 animals are administered a single dose of 100 mg/kg SR9011 (i.p.) and groups of animals (n=6) are sacrificed at CT0, CT6, CT12 and CT18. Gene expression is determined by real time QPCR. |
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References: [1]. Solt LA, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012 Mar 29;485(7396):62-8. |
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IC50: 790 nM for REV-ERB-α; 560 nM for REV-ERB-β
SR9011 is a REV-ERB-α/β agonist.
REV-ERB nuclear receptors have a critical role in feedback regulation of the circadian oscillator. Both Bmal1 and Clock are direct REV-ERB target genes and loss of REV-ERB-α alters circadian behaviour.
In vitro: SR9011 dose-dependently increased the REV-ERB-dependent repressor activity assessed in HEK293 cells. In addition, SR9011 potently and efficaciously suppressed transcription in a cotransfection assay using full-length REV-ERB-a along with a luciferase reporter driven by the Bmal1 promoter. SR9011 also suppressed the expression of BMAL1 messenger RNA in HepG2 cells in a REV-ERB-a/b-dependent manner. Moreover, SR9011 inhibited the activity of the SCNclock, with reversible inhibition of circadian oscillations [1].
In vivo: In the mice under constant darkness conditions, it was observed that the SR9011-dependent decrease in wheel running behaviour was dose-dependent and that the potency (half-maximum effective dose 56 mg/kg) was similar to the potency of SR9011-mediated suppression of a REV-ERB responsive gene, Srebf1, in vivo. Moreover, Tau was not affected by treatment with SR9011, and the recovery after the drug to resume the normal rhythm was similar to the effect observed after removal of the drug from the SCN explants [1].
Clinical trial: Up to now, SR9011 is still in the preclinical development stage.
Reference:
[1] Solt LA,Wang Y,Banerjee S,Hughes T,Kojetin DJ,Lundasen T,Shin Y,Liu J,Cameron MD,Noel R,Yoo SH,Takahashi JS,Butler AA,Kamenecka TM,Burris TP. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature.2012 Mar 29;485(7396):62-8.
| Cas No. | 1379686-29-9 | SDF | |
| 化学名 | 3-(((4-chlorobenzyl)((5-nitrothiophen-2-yl)methyl)amino)methyl)-N-pentylpyrrolidine-1-carboxamide | ||
| Canonical SMILES | CCCCCNC(N1CCC(C1)CN(CC(S2)=CC=C2[N+]([O-])=O)CC3=CC=C(Cl)C=C3)=O | ||
| 分子式 | C23H31ClN4O3S | 分子量 | 479.04 |
| 溶解度 | ≥ 47.9mg/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 | 2.0875 mL | 10.4375 mL | 20.8751 mL |
| 5 mM | 0.4175 mL | 2.0875 mL | 4.175 mL |
| 10 mM | 0.2088 mL | 1.0438 mL | 2.0875 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。