Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Preladenant (SCH-420814) 是一种可口服的竞争性人腺苷 A2A 受体拮抗剂,Ki 为 1.1 nM,比其他腺苷受体选择性高100倍以上。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 266 | 现货 | ||
2 mg | ¥ 378 | 现货 | ||
5 mg | ¥ 619 | 现货 | ||
10 mg | ¥ 993 | 现货 | ||
25 mg | ¥ 1,860 | 现货 | ||
50 mg | ¥ 2,980 | 现货 | ||
100 mg | ¥ 4,560 | 现货 | ||
500 mg | ¥ 9,490 | 现货 |
产品描述 | Preladenant (SCH-420814) is an orally bioavailable antagonist of the adenosine A2A receptor (Ki: 1.1 nM) and has >1000-fold selectivity over all other adenosine receptors. |
靶点活性 | A2A receptor:Ki: 1.1 nM |
体外活性 | In cells expressing the recombinant human A2A receptor, Preladenant completely antagonizes cAMP. The KB values of Preladenant is 1.3 nM at the A2A receptor. A similar functional assay with A2B receptor-expressing cells is used to demonstrate selectivity over A2B receptors. In this assay, the KB value for Preladenant is 1.2 μM and this selectivity for the A2A receptor is 923-fold over the A2B receptor. |
体内活性 | Preladenant (1 mg/kg) inhibits L-Dopa-induced behavioral sensitization. In the mouse tail suspension test and the mouse and rat forced swim test, Preladenant exhibits antidepressant-like profiles. Preladenant dose-dependently reduces the parkinsonian scores at doses of 1 mg/kg (min score: 9.0) and 3 mg/kg (min score: 6.5). A subthreshold dose of Preladenant reduces minimum and mean parkinsonian scores in animals treated with 3 mg kg of L-Dopa to 5.25 and 6.88 respectively. A Wilcoxin test is used to compare individual treatments against the vehicle. Preladenant (3 mg/kg), L-Dopa (3, 6, and 12 mg/kg), and the combination of Preladenant and L-Dopa (1 or 3 mg/kg+3 mg/kg) are all significantly improved on the minimum parkinsonian score. Furthermore, comparable with the 3 mg/kg L-Dopa group, both the 12 mg/kg L-Dopa and L-Dopa+Preladenant groups are markedly improved on both minimal and mean parkinsonian scores. |
激酶实验 | Receptor binding is performed using membranes prepared from cells with recombinant expression of adenosine receptors as follows: human A2A and HEK 293, rat A2A and Chinese hamster ovary, human and rat A1 and Chinese hamster ovary, and human A3 and HEK 293. Radioligand competition binding assays are performed in 96-well plates in a total assay volume of 200 μL using a final test drug concentration range of between 0.1 and 3 μM. Membranes are diluted in assay buffer, pH 7.4 (A1 and A2A, Dulbecco's phosphate-buffered saline with 10 mM MgCl2; A3, 50 mM Tris-HCl, 120 mM NaCl, 10 mM MgCl2). To remove endogenous adenosine from the membrane preparations, 4 U/mL adenosine deaminase is added to the membranes, which are then incubated at room temperature for 15 min. Radioligand is added to a final concentration of 0.5 ([3H]SCH 58261, A2A), 1 ([3H]DPCPX, A1), or 0.25 ([125I]AB-MECA, A3) nM. Nonspecific binding is defined by adding 100 nM CGS 15923 (A2A), 100 nM NECA (A1), or 100 nM DPCPX (A3). Plates are incubated at room temperature with agitation for 1.5 h (A2A and A1) or 2 h (A3). Membranes are filtered onto Packard GF-B filter plates and washed in ice-cold assay buffer using a Brandel cell harvester to separate bound and free radioligand. The plates are dried before addition of 45 μL of Microscint 20 to each well. |
细胞实验 | Preladenant is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].HEK 293 cells stably expressing either human A2A or A2B receptors are grown to confluence, harvested using enzyme-free cell dissociation buffer and pelleted by centrifugation (1000 g; 5 min). The cells are washed and diluted to a final density of 4×106 cells/mL in Hanks' balanced salt solution supplemented with 10 nM HPS, pH 7.4, 5 mM MgCl2, and 0.2% bovine serum albumin. Preladenant is diluted in the above buffer with the inclusion of the following components to achieve the respective final assay concentrations: 0.25% DMSO, 2 U/mL adenosine deaminase, and 100 μM Ro 201724. Cell suspensions (20 μL) are preincubated for 15 min at room temperature in 96-well plates containing 25 μL of vehicle or Preladenant. CGS-21680 (A2A) or 5-N-cyclopropylcarboxamidoadenosine (A2B) at 10-fold the desired concentration is then added, and the reactions are incubated for 15 min at 37°C. The reactions are terminated by the addition of 50 μL of assay/lysis buffer. |
动物实验 | Preladenant is prepared in 50% polyethylene glycol 400 (Rats and Mice).Preladenant is dissolved in cyclodextrin, sonicated and administered p.o. for the study (Monkey).Male CD rats and male CD1 mice are used. Preladenant is administered orally in 50% polyethylene glycol 400 at a dose volume of 3 to 5 mL/kg. In the forced swim test (FST), mice are placed individually into glass cylinders filled to a depth of 10 cm with water (25°C) and left for 6 min. A mouse is judged to be immobile when it floats in an upright position and made only small movements to keep its head above water. The duration of immobility is recorded during the last 4 min of the 6-min testing period by an observer blind to the treatment of the animals. Animals are dosed with vehicle, Preladenant, or SCH 412348 1 h before behavioral testing. Each rat is placed individually in a cylinder of water (25°C) and left to swim for 15 min before being removed and dried in a heated enclosure and returned its home cage. Twenty-four hours later (test day), the animal is re-exposed to the conditions, and the total immobility time during a 5-min period is recorded. In addition, the duration of time that the rats spent climbing the sides of the cylinder is recorded. On test day, each animal is dosed with Preladenant, SCH 412348, or vehicle 1 h before behavioral testing. Six female cynomolgus (Macaca fascicularis) monkeys (weighing 3.5-4.2 kg) are used. The animals are rendered parkinsonian by subcutaneous (sc) administrations of MPTP (2-3 mg/kg) once per week until a stable parkinsonian syndrome (unchanged disability score of 8 or greater for at least a month) developed as measured by a parkinsonian disability scale. At least 2 months after the final administration of MPTP, the monkeys are treated chronically with Prolopa (L-Dopa/benserazide, 100/25 mg) until clear and reproducible dyskinesias developed. The present experiment with L-Dopa and Preladenant (1 mg/kg and 3 mg/kg, p.o.) is performed in these monkeys. |
别名 | SCH-420814, 瑞德南特 |
分子量 | 503.56 |
分子式 | C25H29N9O3 |
CAS No. | 377727-87-2 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
H2O: < 0.1 mg/mL (insoluble)
DMSO: 5 mg/mL (9.93 mM), Sonification is recommended.
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 1.9859 mL | 9.9293 mL | 19.8586 mL | 49.6465 mL |
5 mM | 0.3972 mL | 1.9859 mL | 3.9717 mL | 9.9293 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Preladenant 377727-87-2 GPCR/G Protein Neuroscience Adenosine Receptor SCH 420814 Inhibitor inhibit SCH-420814 瑞德南特 SCH420814 P1 receptor inhibitor