RS 102895 hydrochloride
(Synonyms: RS102895盐酸盐) 目录号 : GC11026
RS 102895 hydrochloride是一种有效的CCR2抑制剂，IC50值为0.36µM。
Cas No.:1173022-16-6
Sample solution is provided at 25 µL, 10mM.
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RS 102895 hydrochloride is a potent inhibitor of CCR2, with an IC50 value of 0.36µM[1]. RS 102895 hydrochloride could specifically bind to the β subunit of CCR2 receptor, effectively inhibit CCR2 signaling and monocyte recruitment[2]. RS 102895 hydrochloride has been widely used to reduce inflammation and delay the progression of hypertension in rat models of hypertension[3].
In vitro, RS 102895 hydrochloride treatment (6µM; 24h) significantly inhibited Monocyte chemotactic protein-3 (MCP-3)-induced human coronary artery smooth muscle cell (CASMC) proliferation[4]. Pretreatment of rat aortic smooth muscle cells (SMCs) with 6μM RS 102895 hydrochloride for 2h partially blocked angiotensin II-stimulated (48h) cell proliferation[5]. Pretreatment of SCC4 cells with RS 102895 hydrochloride (100ng/ml) for 30 minutes inhibited MCP-1-stimulated VEGF-A mRNA expression and protein secretion and reduced cell migration[6].
In vivo, 6-week-old db/db mice fed with a diet supplemented with 2mg/kg/day RS 102895 hydrochloride for 9 weeks improved glucose tolerance, and mesangial expansion, glomerular basement membrane thickening, and enhanced desmin staining were significantly improved in mice[7]. A daily intraperitoneal injection of RS 102895 hydrochloride at a dose of 20mg/kg for 5 consecutive days ameliorated the severity of severe murine experimental autoimmune neuritis model[8]. RS 102895 hydrochloride treatment via intraperitoneal injection at a dose of 5mg/kg/day for 21 days ameliorated renal damage and hypertension of male Dahl SS rats with a high-salt diet[9].
References:
[1] Mirzadegan T, Diehl F, Ebi B, et al. Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helical bundle[J]. Journal of Biological Chemistry, 2000, 275(33): 25562-25571.
[2] Mitchell L A, Hansen R J, Beaupre A J, et al. Optimized dosing of a CCR2 antagonist for amplification of vaccine immunity[J]. International immunopharmacology, 2013, 15(2): 357-363.
[3] Elmarakby A A, Quigley J E, Olearczyk J J, et al. Chemokine receptor 2b inhibition provides renal protection in angiotensin II–salt hypertension[J]. Hypertension, 2007, 50(6): 1069-1076.
[4] Maddaluno M, Di Lauro M V, Di Pascale A, et al. Monocyte chemotactic protein-3 induces human coronary smooth muscle cell proliferation[J]. Atherosclerosis, 2011, 217(1): 113-119.
[5] Yao H L, Gao F H, Li Z Z, et al. Monocyte chemoattractant protein-1 mediates angiotensin II-induced vascular smooth muscle cell proliferation via SAPK/JNK and ERK1/2[J]. Molecular and cellular biochemistry, 2012, 366(1): 355-362.
[6] Lien M Y, Chang A C, Tsai H C, et al. Monocyte chemoattractant protein 1 promotes VEGF-A expression in OSCC by activating ILK and MEK1/2 signaling and downregulating miR-29c[J]. Frontiers in oncology, 2020, 10: 592415.
[7] Seok S J, Lee E S, Kim G T, et al. Blockade of CCL2/CCR2 signalling ameliorates diabetic nephropathy in db/db mice[J]. Nephrology Dialysis Transplantation, 2013, 28(7): 1700-1710.
[8] Yuan F, Yosef N, Lakshmana Reddy C, et al. CCR2 gene deletion and pharmacologic blockade ameliorate a severe murine experimental autoimmune neuritis model of Guillain-Barre syndrome[J]. PloS one, 2014, 9(3): e90463.
[9] Alsheikh A J, Dasinger J H, Abais-Battad J M, et al. CCL2 mediates early renal leukocyte infiltration during salt-sensitive hypertension[J]. American Journal of Physiology-Renal Physiology, 2020, 318(4): F982-F993.
RS 102895 hydrochloride是一种有效的CCR2抑制剂，IC50值为0.36µM[1]。RS 102895 hydrochloride能特异性结合CCR2受体的β亚基，有效抑制CCR2信号通路及单核细胞募集[2]。RS 102895 hydrochloride已广泛应用于高血压大鼠模型中，用于减轻炎症反应及延缓高血压进展[3]。
在体外，使用6µM的RS 102895 hydrochloride处理24小时，可显著抑制单核细胞趋化蛋白-3诱导的人冠状动脉平滑肌细胞(CASMC)增殖[4]。用6μM的RS 102895 hydrochloride预处理大鼠主动脉平滑肌细胞(SMCs) 2小时，能部分阻断血管紧张素II刺激的细胞增殖[5]。以100ng/ml的RS 102895 hydrochloride预处理SCC4细胞30分钟，可抑制单核细胞趋化蛋白-1刺激的VEGF-A mRNA表达及蛋白分泌，并降低细胞迁移能力[6]。
在体内，给6周龄db/db小鼠饲喂添加2mg/kg/day的RS 102895 hydrochloride饮食连续9周，可改善葡萄糖耐受性，并显著减轻系膜扩张、肾小球基底膜增厚等病理改变，同时增强结蛋白染色强度[7]。连续5天每日腹腔注射20mg/kg剂量的RS 102895 hydrochloride，能减轻小鼠实验性自身免疫性神经炎模型的疾病严重程度[8]。通过每日腹腔注射5mg/kg/day剂量的RS 102895 hydrochloride连续21天，可改善高盐饮食雄性Dahl SS大鼠的肾功能损伤及高血压症状[9]。
| Cell experiment [1]: | |
Cell lines | Human coronary artery smooth muscle cell (CASMC) |
Preparation Method | Human CASMCs were cultured in smooth muscle basal medium (SmBM) supplemented with 0.5mg/ml hEGF, 5mg/ml insulin, 1mg/ml hFGF, 50mg/ml gentamicin/amphotericin B, and 5% FBS, and used in all experiments between passages 4 and 8. To quiesce the cells, CASMCs in the exponential growth phase were transferred to SmBM supplemented with 0.1% FBS and incubated for 48h in the absence of growth factors before starting the experiment. CASMCs s were seeded in 96-well plates at a density of 5×103 cells/well. After resting induction, cells were stimulated with human MCP-3 (0.3ng/ml) for 24h in the presence of RS 102895 hydrochloride (6µM) and then incubated with 10µM BrdU for 16h prior to analysis. Human TNF-α (30ng/ml) was used as a positive control. |
Reaction Conditions | 6µM; 24h |
Applications | RS 102895 hydrochloride treatment significantly inhibited MCP-3-induced CASMC proliferation. |
| Animal experiment [2]: | |
Animal models | Male Dahl SS rats |
Preparation Method | Seven-week-old male Dahl SS rats were housed in a temperature and humidity-controlled room with a 12:12h light-dark cycle, and all had ad libitum access to food and water. Rats were divided into two groups: received RS 102895 hydrochloride or vehicle, and were immediately switched from a low-salt diet (0.4% NaCl) to a high-salt diet (4% NaCl) and maintained for 21 days. RS 102895 hydrochloride or DMSO vehicle was intraperitoneally injected daily at a dose of 5mg/kg/day, followed by analysis of mouse kidney tissues and measurement of blood pressure. |
Dosage form | 5mg/kg/day for 21 days; i.p. |
Applications | RS 102895 hydrochloride treatment ameliorated renal damage and hypertension of rats after 21 days of high-salt diet. |
References: | |
| Cas No. | 1173022-16-6 | SDF | |
| 别名 | RS102895盐酸盐 | ||
| 化学名 | 1'-(4-(trifluoromethyl)phenethyl)spiro[benzo[d][1,3]oxazine-4,4'-piperidin]-2-ol hydrochloride | ||
| Canonical SMILES | FC(F)(F)C1=CC=C(CCN2CCC3(C4=CC=CC=C4N=C(O3)O)CC2)C=C1.Cl | ||
| 分子式 | C21H21F3N2O2.HCl | 分子量 | 426.86 |
| 溶解度 | DMF: 25 mg/mL,DMSO: 30 mg/mL,DMSO:PBS(pH 7.2) (1:2): 0.3 mg/mL,Ethanol: 2 mg/mL | 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 | 2.3427 mL | 11.7134 mL | 23.4269 mL |
| 5 mM | 468.5 μL | 2.3427 mL | 4.6854 mL |
| 10 mM | 234.3 μL | 1.1713 mL | 2.3427 mL |
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| 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 |
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| % 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，
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2.
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Quality Control & SDS
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- Purity: >98.00%
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