SR 144528
(Synonyms: SR144528) 目录号 : GC10032
SR 144528是一种高效、选择性且具有口服活性的CB2受体拮抗剂，对 CB2 受体的Ki值为0.6nM。
Cas No.:192703-06-3
Sample solution is provided at 25 µL, 10mM.
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SR 144528 is a highly potent, selective, and orally active antagonist for the CB2 receptor, with a Ki value of 0.6nM [1]. SR 144528 inhibited microsomal ACAT activity in vitro, with an IC50 value of 3.6±1.1μM[2]. SR 144528 has been used for comparative analyses of biased signaling and off-target activity of CB2 receptor ligands[3].
In vitro, SR 144528 pretreatment at 2μM for 1h inhibited apoptosis of Raw 264.7 macrophages following a 16h treatment with 7-ketocholesterol (7KC)[2]. Pretreatment of microglia with 1µM SR 144528 for 15min significantly reduced LPS/IFN-γ (16h)-induced secretion of TNF-α, IL-6, and CCL2, as well as microglial activation[4]. Pretreatment of eosinophilic Eol-1 cells with 10µM SR 144528 for 30min significantly reduced OEA-induced (24h) activation and decreased the mRNA expression of IL-1β, IL-8, IL-5, and IL-13[5].
In vivo, a single dose of SR 144528 (1mg/kg) administered intraperitoneally to male Wistar rats for 30min enhances WIN 55,212-2 (5mg/kg; 24h; i.p.)-induced gastrointestinal motility and gastric emptying[6]. A single intraperitoneal injection of 0.1mg/kg SR 144528 at 30min resulted in a significant reduction in μ-opioid receptor (MOR) mRNA expression in the brains of both CB1 wild-type (CB1+/+) and CB1 cannabinoid receptor knockout mice (CB1−/−) [7]. Intraperitoneal injection of SR 144528 (1mg/kg/day) to C57BL/6J mice once daily for 1 week increased cued fear memory without contextual fear memory[8].
References:
[1] Rinaldi-Carmona M, Barth F, Millan J, et al. SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor[J]. The Journal of pharmacology and experimental therapeutics, 1998, 284(2): 644-650.
[2] Thewke D, Freeman-Anderson N, Pickle T, et al. AM-251 and SR144528 are acyl CoA: cholesterol acyltransferase inhibitors[J]. Biochemical and biophysical research communications, 2009, 381(2): 181-186.
[3] Soethoudt M, Grether U, Fingerle J, et al. Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity[J]. Nature communications, 2017, 8(1): 13958.
[4] Olabiyi B F, Schmoele A C, Beins E C, et al. Pharmacological blockade of cannabinoid receptor 2 signaling does not affect LPS/IFN-γ-induced microglial activation[J]. Scientific Reports, 2023, 13(1): 11105.
[5] Kwon E K, Choi Y, Sim S, et al. Cannabinoid receptor 2 as a regulator of inflammation induced oleoylethanolamide in eosinophilic asthma[J]. Journal of Allergy and Clinical Immunology, 2024, 153(4): 998-1009. e9.
[6] Abalo R, Cabezos P A, Vera G, et al. The cannabinoid antagonist SR144528 enhances the acute effect of WIN 55,212‐2 on gastrointestinal motility in the rat[J]. Neurogastroenterology & Motility, 2010, 22(6): 694-e206.
[7] Páldy E, Bereczki E, Sántha M, et al. CB2 cannabinoid receptor antagonist SR144528 decreases mu-opioid receptor expression and activation in mouse brainstem: role of CB2 receptor in pain[J]. Neurochemistry international, 2008, 53(6-8): 309-316.
[8] Duphare C, Li Y, Kim J. Roles for Type‐2 Cannabinoid Receptors in the Retrieval and Retention of Fear Memory in Mice[J]. The FASEB Journal, 2017, 31: 988.10-988.10.
SR 144528是一种高效、选择性且具有口服活性的CB2受体拮抗剂，对CB2受体的Ki值为0.6nM[1]。SR 144528能在体外抑制微粒体ACAT活性，IC50值为3.6±1.1μM[2]。SR 144528已被用于CB2受体配体的偏向信号传导和脱靶活性的比较分析[3]。
在体外，用2μM的SR 144528预处理Raw 264.7巨噬细胞1小时，能够抑制随后由7-酮胆固醇（7KC）处理16小时所诱导的细胞凋亡[2]。用1µM的SR 144528预处理小胶质细胞15分钟，能显著减少LPS/IFN-γ（处理16小时）诱导的TNF-α、IL-6和CCL2的分泌，并抑制小胶质细胞的活化[4]。用10µM的SR 144528预处理嗜酸性Eol-1细胞30分钟，可显著减弱OEA（处理24小时）诱导的细胞活化，并降低IL-1β、IL-8、IL-5和IL-13的mRNA表达水平[5]。
在体内，向雄性Wistar大鼠单次腹腔注射SR 144528（1mg/kg）30分钟后，能增强WIN 55,212-2（5mg/kg；处理 24 小时；腹腔注射）诱导的胃肠动力和胃排空作用[6]。向CB1野生型（CB1+/+）和CB1大麻素受体基因敲除小鼠（CB1−/−）单次腹腔注射0.1mg/kg剂量的SR 144528 30分钟后，可导致大脑中 μ-阿片受体（MOR） mRNA 表达显著降低 [7]。向C57BL/6J 小鼠每天一次腹腔注射SR 144528（1mg/kg/day），连续一周，能增强线索性恐惧记忆，不影响情境性恐惧记忆[8]。
| Cell experiment [1]: | |
Cell lines | Raw 264.7 macrophages |
Preparation Method | Raw 264.7 macrophages were cultured in RPMI-1640 supplemented with 10% FBS, 2mM glutamine, 100U/ml penicillin, and 100μg/ml streptomycin at 37°C in a humidified atmosphere of 5% CO2 and 95% air. Cells were seeded (2×106/well) in 12-well culture plates. SR 144528 was added at a final concentration of 2μM, 1h prior to the addition of 7KC from a 2mg/ml ethanol stock solution. Controls were adjusted to receive equivalent volumes of DMSO and ethanol. After 16h, caspase-3 activity was determined. |
Reaction Conditions | 2μM; 1h |
Applications | SR 144528 treatment inhibited the caspase-3 activity in Raw 264.7 macrophages after 7KC stimulation. |
| Animal experiment [2]: | |
Animal models | Rag-2−/− mice |
Preparation Method | Tumors were induced by subcutaneous inoculation of 5×106 C6 glioma cells in Rag-2−/− mice supplemented with 0.1% glucose in PBS. When the mean tumor volume reached 250mm3 (range, 200 to 300mm3), mice were randomly assigned to receive intratumoral injection of vehicle, 50μg/100μl SR 144528 (50μg of SR144528 dissolved in 100μl of PBS), JWH-133 (50μg/100μl), and JWH-133+ SR 144528 (50μg/100μl), respectively, over 8 days. The tumor was measured with an external caliper, and the volume was calculated as (4π/3) × (width /2)2 × (length /2). |
Dosage form | 50μg/100μl/day for 8 days; intratumoral injection |
Applications | SR 144528 treatment prevented JWH-133-induced tumor regression in mice. |
References: | |
| Cas No. | 192703-06-3 | SDF | |
| 别名 | SR144528 | ||
| 化学名 | 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide | ||
| Canonical SMILES | C[C@]1(C2)[C@H](NC(C3=NN(CC4=CC=C(C)C=C4)C(C5=CC(C)=C(Cl)C=C5)=C3)=O)C(C)(C)[C@@H]2CC1 | ||
| 分子式 | C29H34ClN3O | 分子量 | 475.2 |
| 溶解度 | ≤30mg/ml in ethanol;20mg/ml in DMSO;30mg/ml in dimethyl formamide | 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 | 2.1044 mL | 10.5219 mL | 21.0438 mL |
| 5 mM | 420.9 μL | 2.1044 mL | 4.2088 mL |
| 10 mM | 210.4 μL | 1.0522 mL | 2.1044 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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- Purity: >98.00%
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