Reparixin
(Synonyms: 瑞帕利辛; Repertaxin; DF 1681Y) 目录号 : GC12849
Reparixin是CXCL8受体CXCR1和CXCR2的非竞争性变构抑制剂，IC50值分别为1nM和100nM。
Cas No.:266359-83-5
Sample solution is provided at 25 µL, 10mM.
Reparixin is a noncompetitive allosteric inhibitor of the CXCL8 receptors CXCR1 and CXCR2, with IC50 values of 1nM and 10nM, respectively[1]. CXCR1 and CXCR2 are G protein-coupled receptors (GPCRs) that bind with high affinity to glutamine-leucine-arginine-positive (ELR+) chemokines. Blocking GPCRs appears to be an effective therapeutic strategy for treating ischemia/reperfusion injury. Therefore, reparixin is commonly used in the treatment and research of diseases such as acute lung injury, peritonitis, traumatic spinal cord injury and ischemia[2,3].
In vitro, treatment of undifferentiated human thyroid cancer 8505c and CAL62 cells with reparixin (10-30μM) for 8 days significantly inhibited cancer cell proliferation and reduced cell viability in a dose-dependent manner, while showing no significant effect on non-malignant thyroid cells[4]. Treatment of growth factor-deprived degenerating human MN (motor neuron)-like cells with reparixin (10μM) for 48h rescued glial cells from apoptosis and maintained neuronal morphology[5].
In vivo, reparixin (15mg/kg/day; twice a day) was administered to Sprague-Dawley rats with traumatic spinal cord injury (SCI) via initial intravenous injection followed by subcutaneous injections. After 7 days, reparixin significantly reduced the number of ED-1-positive cells at the injury site and decreased the expression of pro-inflammatory cytokines such as MIP-2 and TNF-α[6]. reparixin (30mg/kg/day; twice a day) was administered via intraperitoneal injection to CD1 nu/nu mice xenografted with 8505c thyroid cancer (TC) cells. After 4 weeks, tumor volume was significantly reduced[4]. Reparixin (15μg/g) was administered via intraperitoneal injection to C57BL/6 mice 15min before and 2h after lipopolysaccharide (LPS)-induced pulmonary inflammation, which significantly reduced neutrophil recruitment into the alveolar space after 24h[7].
References:
[1] BERTINI R, ALLEGRETTI M, BIZZARRI C, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury[J]. Proceedings of the National Academy of Sciences, 2004, 101(32): 11791-11796.
[2] KIM H Y, CHOI J H, KANG Y J, et al. reparixin, an inhibitor of CXCR1 and CXCR2 receptor activation, attenuates blood pressure and hypertension-related mediators expression in spontaneously hypertensive rats[J]. Biological and Pharmaceutical Bulletin, 2011, 34(1): 120-127.
[3] THITIWUTHIKIAT P, TA-UEA T, PONGHAN T, et al. The protective effects of reparixin against endothelial ischemia-reperfusion injury[J]. International Journal of Health Sciences, 2022, 16(3): 20.
[4] LIOTTI F, DE PIZZOL M, ALLEGRETTI M, et al. Multiple anti-tumor effects of reparixin on thyroid cancer[J]. Oncotarget, 2017, 8(22): 35946.
[5] LA COGNATA V, GOLINI E, IEMMOLO R, et al. CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice[J]. Neurobiology of Disease, 2021, 160: 105538.
[6] GORIO A, MADASCHI L, ZADRA G, et al. Reparixin, an inhibitor of CXCR2 function, attenuates inflammatory responses and promotes recovery of function after traumatic lesion to the spinal cord[J]. The Journal of Pharmacology and Experimental Therapeutics, 2007, 322(3): 973-981.
[7] ZARBOCK A, ALLEGRETTI M, LEY K. Therapeutic inhibition of CXCR2 by Reparixin attenuates acute lung injury in mice[J]. British journal of pharmacology, 2008, 155(3): 357-364.
Reparixin是CXCL8受体CXCR1和CXCR2的非竞争性变构抑制剂，IC50值分别为1nM和100nM[1]。CXCR1和CXCR2是G蛋白偶联受体（GPCR），以高亲和力结合glutamine-leucine-arginine-positive（ELR+）趋化因子，而阻断GPCR似乎是治疗缺血/再灌注损伤的有效治疗策略，故reparixin常被用于急性肺损伤、腹膜炎及创伤性脊髓损伤和缺血等疾病的治疗和研究[2,3]。
在体外，reparixin（10-30μM）处理人未分化甲状腺癌8505c和CAL62细胞8天，能以剂量依赖性方式显著抑制癌细胞的增殖并降低细胞活力，但对非恶性甲状腺细胞无显著影响[4]。Reparixin（10μM）处理生长因子剥夺的退化类人运动神经元（motor neuronal, MN）细胞48h，可挽救神经胶质细胞免于凋亡并维持神经元形态[5]。
在体内，reparixin（15mg/kg/day; twice a day）通过首次静脉给药，后续皮下注射的方式治疗创伤性脊髓损伤（SCI）的Sprague-Dawley大鼠，7天后显著减少了损伤部位ED-1阳性细胞的数量，降低了促炎细胞因子MIP-2和TNF-α等的表达[6]。Reparixin（30mg/kg/day; twice a day）通过腹膜注射治疗异种移植了8505c甲状腺癌（TC）细胞的CD1 nu/nu小鼠，4周后肿瘤的体积显著减小[4]。Reparixin（15μg/g）分别于脂多糖LPS诱发C57BL/6小鼠肺部炎症前15min和炎症后2h通过腹腔注射给药，24h后显著地减少了中性粒细胞向肺泡腔的募集[7]。
| Cell experiment [1]: | |
Cell lines | 8505c and CAL62 (human thyroid cell lines) |
Preparation Method | 8505c and CAL62 cell lines (derived from human ATCs) were chosen as representative of undifferentiated and aggressive Thyroid cancer (TC) cells. The growth rates of these cell lines were measured in complete medium (DMEM 10% FBS) in the presence or absence of different concentrations of reparixin (0.1μM, 1μM, 10μM, and 30μM). |
Reaction Conditions | 0.1, 1, 10, and 30μM; 8 days |
Applications | Reparixin inhibited 8505c and CAL62 cell growth in a dose-dependent manner after 8 days of culture. No significant effects were observed at 1μM and 0.1μM of reparixin in all the cell lines tested. This effect was not observed in non-malignant thyroid cells, where a limited toxic effect was observed only after 10 days of treatment with 30μM reparixin, being it significantly lower than that observed in TC cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 (Mouse model of LPS-induced pulmonary inflammation) |
Preparation Method |
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Dosage form | 3, 15, 30μg/g; i.p. |
Applications | Dose-dependent inhibition of neutrophil recruitment into the lung following LPS inhalation. Treatment with 3μg/g Reparixin did not reduce neutrophil recruitment into the lung, whereas 15μg/g led to a significant reduction in neutrophil recruitment into the alveolar space. |
References: | |
| Cas No. | 266359-83-5 | SDF | |
| 别名 | 瑞帕利辛; Repertaxin; DF 1681Y | ||
| 化学名 | (2R)-2-[4-(2-methylpropyl)phenyl]-N-methylsulfonylpropanamide | ||
| Canonical SMILES | CC(C)CC1=CC=C(C=C1)C(C)C(=O)NS(=O)(=O)C | ||
| 分子式 | C14H21NO3S | 分子量 | 283.39 |
| 溶解度 | ≥ 14.15 mg/mL in DMSO, ≥ 47.3 mg/mL in EtOH | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5287 mL | 17.6435 mL | 35.2871 mL |
| 5 mM | 705.7 μL | 3.5287 mL | 7.0574 mL |
| 10 mM | 352.9 μL | 1.7644 mL | 3.5287 mL |
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