GR 46611是一种5-HT1B和5-HT1D受体激动剂，可调节动物的摄食行为。
Cas No.:185259-85-2
Sample solution is provided at 25 µL, 10mM.
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GR 46611 is a 5-HT1B and 5-HT1D receptor agonist, which can regulate the feeding behavior of animals[1]. GR 46611 enhances transporter ZnT8-dependent zinc import into insulin granules through stimulation of V-ATPase-driven acidification in β-cells and increases β-cell zinc content and augments β-cell-targeted drug delivery [2]. GR 46611 has been widely used in rat formalin tests to alleviate inflammatory pain [3].
In vitro, GR 46611 treatment (1μM) for 48 hours significantly promoted the proliferation of CCRF-CEM cells[4].
In vivo, GR 46611 treatment via daily intraperitoneal injection at a dose of 1mg/kg for 14 days significantly increased the seizure threshold of Dravet syndrome (DS) mice induced by hyperthermia, and reduced the severity of seizures and increased the survival rate of the mice[5]. A single injection of GR 46611 (30mg/kg) was administered, lasting for 3 hours, which significantly caused a decrease in rectal temperature in adult guinea pigs[6]. A single injection of GR 46611 (0.6nM; 1µl) via anterior portion of paraventricular thalamic nucleus reduced the pain threshold of mice within 24 hours and prolonged the immobility time in the forced swimming test (FST) and tail suspension test (TST)[7].
References:
[1] Da Silva R A, de Oliveira S T, Hackl L P N, et al. Ingestive behaviors and metabolic fuels after central injections of 5-HT1A and 5-HT1D/1B receptors agonists in the pigeon[J]. Brain research, 2004, 1026(2): 275-283.
[2] Lee S, Fraser H P, Schugar R C, et al. Pharmacologic stimulation of insulin granule acidification increases β-cell zinc content and augments β-cell-targeted drug delivery[J]. Journal of Biological Chemistry, 2025, 301(10).
[3] Granados-Soto V, Argüelles C F, Rocha-González H I, et al. The role of peripheral 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F serotonergic receptors in the reduction of nociception in rats[J]. Neuroscience, 2010, 165(2): 561-568.
[4] Sibella-Argüelles C. The proliferation of human T lymphoblastic cells induced by 5-HT1B receptors activation is regulated by 5-HT-moduline[J]. Comptes Rendus de l'Académie des Sciences-Series III-Sciences de la Vie, 2001, 324(4): 365-372.
[5] Hatini P G, Commons K G. A 5‐HT1D‐receptor agonist protects Dravet syndrome mice from seizure and early death[J]. European Journal of Neuroscience, 2020, 52(10): 4370-4374.
[6] Skingle M, Higgins G A, Feniuk W. Stimulation of central 5-HT1D receptors causes hypothermia in the guinea-pig[J]. Journal of Psychopharmacology, 1994, 8(1): 14-21.
[7] Cui M, Ji R, Song L, et al. Neuronal and molecular mechanisms underlying chronic pain and depression comorbidity in the paraventricular thalamus[J]. Journal of Neuroscience, 2024, 44(13).
GR 46611是一种5-HT1B和5-HT1D受体激动剂，可调节动物的摄食行为[1]。GR 46611通过刺激β细胞中V-ATP酶驱动的酸化作用，增强转运蛋白ZnT8依赖的锌向胰岛素颗粒的输入，增加β细胞锌含量，并增强β细胞靶向药物的递送[2]。GR 46611已被广泛用于大鼠福尔马林试验中以减轻炎性疼痛[3]。
在体外，1μM的GR 46611处理CCRF-CEM细胞48小时，显著促进了细胞增殖[4]。
在体内，每日腹腔注射1mg/kg剂量的GR 46611，持续14天，显著提高了Dravet syndrome (DS)小鼠由高热诱导的癫痫发作阈值，降低了癫痫发作的严重程度，并提高了小鼠的存活率[5]。单次注射30mg/kg剂量的GR 46611，持续3小时，显著降低了成年豚鼠的直肠温度[6]。通过丘脑室旁核前部单次注射GR 46611（0.6nM；1μl），在24小时内降低了小鼠的疼痛阈值，并延长了强迫游泳试验(FST)和悬尾试验(TST)中的不动时间[7]。
| Cell experiment [1]: | |
Cell lines | CCRF CEM cells |
Preparation Method | CCRF CEM cells were cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum, 100U/ml penicillin, 100μg/ml streptomycin in a humidified incubator at 37°C and 5% CO2. CCRF CEM cells were plated at a density of 2×105 cells/well in a 6-well plate with growth medium for 24h, and then were incubated with 1μM GR 46611 for 48h, the cell proliferation was analyzed. |
Reaction Conditions | 1μM; 48h |
Applications | GR 46611 treatment significantly enhanced cell proliferation of CCRF CEM cells. |
| Animal experiment [2]: | |
Animal models | Dravet syndrome (DS) mice |
Preparation Method | DS mice were primed with a hyperthermia-induced seizure on postnatal day of age (P) 18±1 day. After a 5-min acclimation to a RET-3 rectal temperature probe, body temperature was raised at a rate of 0.25°C per minute using a heat lamp until the first generalized seizure resulting in a loss of posture. Subsequently, the same mice were tested for seizure threshold at P21 after receiving drug pretreatment (GR 46611 was dissolved in 5% DMSO, 30% propylene glycol in saline and administered intraperitoneally at 1mg/kg) 20min before repeating the hyperthermia protocol. |
Dosage form | 1mg/kg for once; i.p. |
Applications | GR 46611 treatment increased the threshold of hyperthermia-induced seizure and lowered seizure severity in DS mice. |
References: | |
| Cas No. | 185259-85-2 | SDF | |
| 化学名 | (Z)-3-(3-(2-(dimethylamino)ethyl)-1H-indol-5-yl)-N-(4-methoxybenzyl)acrylamide | ||
| Canonical SMILES | O=C(/C=C\C1=CC=C2NC=C(C2=C1)CCN(C)C)NCC(C=C3)=CC=C3OC | ||
| 分子式 | C23H27N3O2 | 分子量 | 377.49 |
| 溶解度 | Soluble to 50 mM in DMSO and to 10 mM in ethanol | 储存条件 | Store at RT |
| 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 | 2.6491 mL | 13.2454 mL | 26.4908 mL |
| 5 mM | 529.8 μL | 2.6491 mL | 5.2982 mL |
| 10 mM | 264.9 μL | 1.3245 mL | 2.6491 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。
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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