DAA-1106
(Synonyms: N-(2,5-二甲氧基苄基)-N-(5-氟-2-苯氧基苯基)乙酰胺) 目录号 : GC30930
A TSPO agonist
Cas No.:220551-92-8
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
DAA1106 is an agonist of the 18 kDa translocator protein TSPO, which was previously known as the peripheral benzodiazepine receptor (PBR), that has an IC50 value of 0.28 nM in a radioligand binding assay.1 It is selective for TSPO over central benzodiazepine receptors (CBRs) and GABAA receptors in rat whole brain membranes, as well as a panel of 54 ion channels, uptake/transporters, and secondary messenger receptors at concentrations greater than 10 ?M. DAA1106 increases mitochondrial prognenolone formation in rat brain homogenates, which indirectly potentiates GABAA receptor signaling. DAA1106 (1-10 mg/kg) increases the time mice spend in the light area of the light/dark exploration and the time rats spend in open arms of the elevated plus maze in a dose-dependent manner, suggesting a decrease in anxiety-like behavior. Various radiolabeled versions of DAA1106 have been synthesized to study the distribution of PBRs in neurological disease models using positron emission tomography (PET).2,3
1.Okuyama, S., Chaki, S., Yoshikawa, R., et al.Neuropharmacological profile of peripheral benzodiazepine receptor agonists, DAA1097 and DAA1106Life Sci.64(16)1455-1464(1999) 2.Zhang, M.-R., Kida, T., Noguchi, J., et al.[11C]DAA1106: radiosynthesis and in vivo binding to peripheral benzodiazepine receptors in mouse brainNucl. Med. Biol.30(5)513-519(2003) 3.Venneti, S., Wagner, A.K., Wang, G., et al.The high affinity peripheral benzodiazepine receptor ligand DAA1106 binds specifically to microglia in a rat model of traumatic brain injury: Implications for PET imagingExp. Neurol.207(1)118-127(2007)
| Cas No. | 220551-92-8 | SDF | |
| 别名 | N-(2,5-二甲氧基苄基)-N-(5-氟-2-苯氧基苯基)乙酰胺 | ||
| Canonical SMILES | CC(N(CC1=CC(OC)=CC=C1OC)C2=CC(F)=CC=C2OC3=CC=CC=C3)=O | ||
| 分子式 | C23H22FNO4 | 分子量 | 395.42 |
| 溶解度 | DMSO : ≥ 35 mg/mL (88.51 mM) | 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 | 2.529 mL | 12.6448 mL | 25.2896 mL |
| 5 mM | 0.5058 mL | 2.529 mL | 5.0579 mL |
| 10 mM | 0.2529 mL | 1.2645 mL | 2.529 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。
Insights into Cholesterol/Membrane Protein Interactions Using Paramagnetic Solid-State NMR
Cholesterol is an essential component of animal cell membranes and impacts the structure and function of membrane proteins. But how cholesterol exerts its functions remains often enigmatic. Here, high-resolution solid-state NMR in combination with paramagnetic cholesterol analogues was shown to be a powerful approach to study the interaction of membrane proteins with cholesterol. Application of the method to the 169-residue translocator protein TSPO provides residue-specific information about its interaction with cholesterol. Comparison with NMR signal perturbations induced by diamagnetic cholesterol furthermore supports changes in the structure of mammalian TSPO caused by cholesterol binding.
Synthesis of (18) F-Difluoromethylarenes from Aryl (Pseudo) Halides
A general method for the synthesis of [(18) F]difluoromethylarenes from [(18) F]fluoride for radiopharmaceutical discovery is reported. The method is practical, operationally simple, tolerates a wide scope of functional groups, and enables the labeling of a variety of arenes and heteroarenes with radiochemical yields (RCYs, not decay-corrected) from 10 to 60 %. The (18) F-fluorination precursors are readily prepared from aryl chlorides, bromides, iodides, and triflates. Seven (18) F-difluoromethylarene drug analogues and radiopharmaceuticals including Claritin, fluoxetine (Prozac), and [(18) F]DAA1106 were synthesized to show the potential of the method for applications in PET radiopharmaceutical design.
Fully automated synthesis of PET TSPO radioligands [11C]DAA1106 and [18F]FEDAA1106
[(11)C]DAA1106 was prepared by O-[(11)C]methylation of DAA1123 with [(11)C]CH(3)OTf and NaH in CH(3)CN at 80°C and isolated by HPLC combined with SPE purification in 60-70% decay corrected radiochemical yield. [(18)F]FEDAA1106 was synthesized by the nucleophilic substitution of tosyloxy-FEDAA1106 in DMSO with K[(18)F]F/Kryptofix 2.2.2 at 140°C and isolated by HPLC combined with SPE purification in 30-60% decay corrected radiochemical yield. The specific activity for [(11)C]DAA1106 and [(18)F]FEDAA1106 was 370-740GBq/μmol and 37-222GBq/μmol at EOB, respectively.
Positron Emission Tomography Imaging of Long-Term Expression of the 18 kDa Translocator Protein After Sudden Cardiac Arrest in Rats
Background: Knowledge about the neuroinflammatory state during months after sudden cardiac arrest is scarce. Neuroinflammation is mediated by cells that express the 18 kDa translocator protein (TSPO). We determined the time course of TSPO-expressing cells in a rat model of sudden cardiac arrest using longitudinal in vivo positron emission tomography (PET) imaging with the TSPO-specific tracer [18F]DAA1106 over a period of 6 months.
Methods: Five male Sprague Dawley rats were resuscitated from 6 min sudden cardiac arrest due to ventricular fibrillation, three animals served as shams. PET measurements were performed on day 5, 8, 14, 90, and 180 after intervention. Magnetic resonance imaging was performed on day 140. Imaging was preceded by Barnes Maze spatial memory testing on day 3, 13, 90, and 180. Specificity of [18F]DAA1106 binding was confirmed by Iba-1 immunohistochemistry.
Results: [18F]DAA1106 accumulated bilaterally in the dorsal hippocampus of all sudden cardiac arrest animals on all measured time points. Immunohistochemistry confirmed Iba-1 expressing cells in the hippocampal CA1 region. The number of Iba-1-immunoreactive objects per mm2 was significantly correlated with [18F]DAA1106 uptake. Additionally, two of the five sudden cardiac arrest rats showed bilateral TSPO-expression in the striatum that persisted until day 180. In Barnes Maze, the relative time spent in the target quadrant negatively correlates with dorsal hippocampal [18F]DAA1106 uptake on day 14 and 180.
Conclusions: After sudden cardiac arrest, TSPO remains expressed over the long-term. Sustainable treatment options for neuroinflammation may be considered to improve cognitive functions after sudden cardiac arrest.
Combined CB2 receptor agonist and photodynamic therapy synergistically inhibit tumor growth in triple negative breast cancer
Triple negative breast cancer (TNBC) is the deadliest form of breast cancer because it is more aggressive, diagnosed at later stage and more likely to develop local and systemic recurrence. Many patients do not experience adequate tumor control after current clinical treatments involving surgical removal, chemotherapy and/or radiotherapy, leading to disease progression and significantly decreased quality of life. Here we report a new combinatory therapy strategy involving cannabinoid-based medicine and photodynamic therapy (PDT) for the treatment of TNBC. This combinatory therapy targets two proteins upregulated in TNBC: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the combined CB2R agonist and TSPO-PDT treatment resulted in synergistic inhibition in TNBC cell and tumor growth. This combinatory therapy approach provides new opportunities to treat TNBC with high efficacy. In addition, this study provides new evidence on the therapeutic potential of CB2R agonists for cancer.