SAE-14
(Synonyms: GPR183 antagonist-1) 目录号 : GC65986
SAE-14 (compound SAE-14) 是一种有效、特异的 GPR183 拮抗剂，IC50值为 28.5 nM，可抑制 HL-60 细胞中 7α, 25-OHC 诱导的钙信号转导， IC50 值低于 50 nM。SAE-14 可逆转小鼠的异位性疼痛。
Cas No.:1241280-25-0
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
IC50: 28.5 nM (GPR183)[1]
SAE-14 (compound SAE-14) is a potent, specific GPR183 antagonist with an IC50 value of 28.5 nM, can antagonize 7α, 25-OHC-induced calcium mobilization with IC50 value below 50 nM in HL-60 cells. GPR183 antagonist-1 can reverse allodynia in mice[1].
SAE-14 (compound SAE-14) can able to antagonize 7α, 25-OHC-induced calcium mobilization with an IC50 value below 50 nM[1].
Cell Viability Assay[1]
| Cell Line: | The human leukemia (HL)-60 cells |
| Concentration: | 5×of the antagonist |
| Incubation Time: | 15 min |
| Result: | Had GPR183-specific (IC50: 28.5nM) and abolished 7a, 25-OHC-induced calcium mobilization in the HL-60 cells. |
SAE-14 (compound SAE-14) (i.th.; 2.9 µM; once) can reverse nerve injury-induced allodynia in mice[1].
| Animal Model: | Male and female ICR mice[1] |
| Dosage: | 2.9 µM |
| Administration: | intrathecal (i.th.) injections; 2.9 µM; once |
| Result: | Reversed CCI-induced mechanical allodynia in a time-dependent manner. |
| Cas No. | 1241280-25-0 | SDF | Download SDF |
| 别名 | GPR183 antagonist-1 | ||
| 分子式 | C19H19F3N2O2 | 分子量 | 364.36 |
| 溶解度 | DMSO : 100 mg/mL (274.45 mM; ultrasonic and warming and heat to 60°C) | 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 | 2.7445 mL | 13.7227 mL | 27.4454 mL |
| 5 mM | 0.5489 mL | 2.7445 mL | 5.4891 mL |
| 10 mM | 0.2745 mL | 1.3723 mL | 2.7445 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。
Activation of GPR183 by 7 α,25-Dihydroxycholesterol Induces Behavioral Hypersensitivity through Mitogen-Activated Protein Kinase and Nuclear Factor- κ B
J Pharmacol Exp Ther 2022 Nov;383(2):172-181.PMID:36116795DOI:10.1124/jpet.122.001283
Emerging evidence implicates the G-protein coupled receptor (GPCR) GPR183 in the development of neuropathic pain. Further investigation of the signaling pathways downstream of GPR183 is needed to support the development of GPR183 antagonists as analgesics. In rodents, intrathecal injection of its ligand, 7α,25-dihydroxycholesterol (7α,25-OHC), causes time-dependent development of mechano-and cold- allodynia (behavioral hypersensitivity). These effects are blocked by the selective small molecule GPR183 antagonist, SAE-14. However, the molecular mechanisms engaged downstream of GPR183 in the spinal cord are not known. Here, we show that 7α,25-OHC-induced behavioral hypersensitivity is Gα i dependent, but not β-arrestin 2-dependent. Non-biased transcriptomic analyses of dorsal-horn spinal cord (DH-SC) tissues harvested at the time of peak hypersensitivity implicate potential contributions of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB). In support, we found that the development of 7α,25-OHC/GPR183-induced mechano-allodynia was associated with significant activation of MAPKs (extracellular signal-regulated kinase [ERK], p38) and redox-sensitive transcription factors (NF-κB) and increased formation of inflammatory and neuroexcitatory cytokines. SAE-14 blocked these effects and behavioral hypersensitivity. Our findings provide novel mechanistic insight into how GPR183 signaling in the spinal cord produces hypersensitivity through MAPK and NF-κB activation. SIGNIFICANCE STATEMENT: Using a multi-disciplinary approach, we have characterized the molecular mechanisms underpinning 7α,25-OHC/GPR183-induced hypersensitivity in mice. Intrathecal injections of the GPR183 agonist 7α,25-OHC induce behavioral hypersensitivity, and these effects are blocked by the selective GPR183 antagonist SAE-14. We found that 7α,25-OHC-induced allodynia is dependent on MAPK and NF-κB signaling pathways and results in an increase in pro-inflammatory cytokine expression. This study provides a first insight into how GPR183 signaling in the spinal cord is pronociceptive.