Antalarmin，一种吡咯嘧啶，是一种有效的小分子非肽CRF1（促肾上腺皮质激素释放因子受体1）的选择性受体拮抗剂。
Cas No.:157284-96-3
Sample solution is provided at 25 µL, 10mM.
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Antalarmin, a pyrrolopyrimidine, is a potent, small molecule, nonpeptide CRF1 (Corticotropin-Releasing Factor Receptor 1) selective receptor antagonist. Antalarmin exhibits high affinity for the CRF1 (Ki=2.7nM), but not CRF2 receptor as determined in Lt-K-mouse fibroblast cells[1].
In vitro, Antalarmin (100nM) treatment for 48 hours blocked CRF-induced increases in PKAIIβ levels in primary hippocampal neurons derived from Tg2576 mice[2].
In vivo, intraperitoneal administration of Antalarmin at doses of 5, 10, and 20mg/kg for 7 days produced dose-dependent decreases in Aβ1-42 levels in Tg2576 mice[2]. Furthermore, treatment with Antalarmin at 20mg/kg for 6 months significantly reduced Aβ1-42 levels and Aβ plaque deposition in the cortex of Tg2576 mice[2]. In BALB/cByJIco male mice, intraperitoneal administration of Antalarmin at 10mg/kg daily for 4 weeks significantly improved the physical state of the mice and induced a nonsignificant decrease in time spent in the lit box (TLB) and activity[3].
References:
[1] Zorrilla EP, Schulteis G, Ormsby A, et al. Urocortin shares the memory modulating effects of corticotropin-releasing factor (CRF): mediation by CRF1 receptors. Brain Res. 2002;952(2):200-210.
[2] Dong H, Wang S, Zeng Z, et al. Effects of corticotrophin-releasing factor receptor 1 antagonists on amyloid-β and behavior in Tg2576 mice. Psychopharmacology (Berl). 2014;231(24):4711-4722.
[3] Ducottet C, et al. Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist antalarmin in the chronic mild stress model of depression in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Jun;27(4):625-31.
Antalarmin，一种吡咯嘧啶，是一种有效的小分子非肽CRF1（促肾上腺皮质激素释放因子受体1）的选择性受体拮抗剂。在Lt-K小鼠成纤维细胞中，Antalarmin对CRF1具有高亲和力（Ki=2.7nM），但对CRF2受体没有亲和力[1]。
体外实验中，Antalarmin（100nM）处理48小时可阻断CRF诱导的Tg2576小鼠海马原代神经元PKAIIβ水平升高[2]。
体内实验中，在Tg2576小鼠中，腹腔注射Antalarmin（5、10 和 20mg/kg）连续给药7天，可剂量依赖性地降低Aβ1-42水平。此外，以20mg/kg剂量给予Antalarmin持续6个月，可显著降低Tg2576小鼠皮层中的Aβ1-42水平及Aβ斑块沉积[2]。在BALB/cByJIco雄性小鼠中，每天以10mg/kg的剂量腹腔注射Antalarmin，连续4周显著改善了小鼠的身体状态，且不影响小鼠在点亮盒（TLB）中的时间和活动[3]。
| Cell experiment [1]: | |
Cell lines | Primary hippocampal neurons derived from Tg2576 mice |
Preparation Method | Cells were maintained in neurobasal medium supplemented with B-27, 2mM glutamine, 100μg/mL of streptomycin, and penicillin in the incubator at 37°C in a humidified atmosphere of 95% air and 5% CO2. Cultured neurons were treated at day 14 with different doses of CRF (0.1, 1 and 10nM), Antalarmin (100nM), and PKA inhibitor H-89 (1μM). The levels of α-β1-42 and PKAIIβ in hippocampal neurons of Tg2576 mice after 48 hours of exposure to CRF, antalarmin, and H-89 were detected by ELISA and Western blot. |
Reaction Conditions | 100nM; 48h |
Applications | Western blotting analysis indicated that CRF significantly increased PKAIIβ expression, and Antalarmin could block this effect. |
| Animal experiment [1]: | |
Animal models | Tg2576 mice |
Preparation Method | Sub-acute stress paradigm: Mice were given Antalarmin (suspended in warm water with 20% Tween-80) at one of 3 doses (5, 10 and 20mg/kg) by intraperitoneal (IP) injection once a day for 7 days. Chronic stress paradigm: Antalarmin (20mg/kg) was suspended in drinking water for drug administration (first suspended in warm water with 20% Tween-80, then diluted in drinking water) and the final concentration of Tween-80 in the drinking water is 0.2% for 6 months. |
Dosage form | 5, 10 and 20mg/kg/d; 7d or 6m; i.p. |
Applications | 7 days: Administration of Antalarmin showed dose-dependent decreases of Aβ1-42 levels in isolated mice. 6 months: Chronic administration of Antalarmin (20mg/kg) significantly decreased Aβ1-42 levels and Aβ plaque deposition in the cortex. |
References: | |
| Cas No. | 157284-96-3 | SDF | |
| 分子式 | C24H34N4 | 分子量 | 378.55 |
| 溶解度 | DMSO : 25 mg/mL (66.04 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6417 mL | 13.2083 mL | 26.4166 mL |
| 5 mM | 528.3 μL | 2.6417 mL | 5.2833 mL |
| 10 mM | 264.2 μL | 1.3208 mL | 2.6417 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。
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Quality Control & SDS
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- Purity: >97.00% Appearance: A solid
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