Customer Validation
- •Ann Rheum Dis. 2016 Apr;75(4):730-8.
- •Nat Commun. 2017 May 26;8:15584.
- •Cell Death Dis. 2017 Jul 13;8(7):e2932.
- •Stem Cells. 2015 Dec;33(12):3558-68.
- •Biochim Biophys Acta. 2017 Jan;1863(1):220-230.
- •Oncotarget. 2017 Jul 21;8(36):60210-60222.
- •Oncogenesis. 2016 Jun 13;5(6):e234.
- •J Gastroenterol Hepatol. 2017 May 8.
- •Vet Immunol Immunopathol. 2016 Dec;182:52-58.
Description |
Reparixin is a potent inhibitor of both CXCL8 receptors CXCR1/2, it inhibits weakly CXCR2-mediated cell migration (IC50=100 nM), whereas it strongly blocks CXCR1-mediated chemotaxis (IC50=1 nM). |
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IC50 & Target |
IC50: 5.6/80 nM (CXCR1wt/CXCR1Ile43Val, in L1.2 cell)[1] |
In Vitro |
Reparixin is a potent functional inhibitor of CXCL8-induced biological activities on human PMNs with a marked selectivity (around 400-fold) for CXCR1, as shown in specific experiments on CXCR1/L1.2 and CXCR2/L1.2 transfected cells and on human PMNs. The efficacy of Reparixin is significantly lower in L1.2 cells expressing Ile43Val CXCR1 mutant (IC50 values of 5.6 nM and 80 nM for CXCR1 wt and CXCR1 Ile43Val, respectively)[1]. Reparixin is a non-competitive allosteric inhibitor of IL-8 receptors with a 400-fold higher efficacy in inhibiting CXCR1 activity than CXCR2[2]. |
In Vivo |
Reparixin is an inhibitor of CXCL8 receptor CXCR1 and CXCR2 activation, has been shown to attenuate inflammatory responses in various injury models. Spontaneously hypertensive rats (SHR) are administered a subcutaneous injection of Reparixin (5 mg/kg) daily for 3 weeks. Reparixin effectively decreases systolic blood pressure and increased the blood flow[3]. Reparixin reduces the levels of IL-1β in the brain after middle cerebral artery occlusion/reperfusion (MCAo) in mice. Bars represent levels of IL-1β (pg/100 mg) measured by ELISA in the brain tissues of mice subjected or not (SHAM) to MCAo and pretreated with vehicle or Reparixin (30 mg/kg, s.c.)[4]. |
References |
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Preparing Stock Solutions |
Please refer to the solubility information to select the appropriate solvent.
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Cell Assay
[1] |
Reparixin is dissolved in saline at the appropriate dilution[1]. L1.2 Cell suspension (1.5-3×106 cells/mL) is incubated at 37°C for 15 min in the presence of vehicle or of Reparixin (1 nM-1μM) and next seeded in triplicates in the upper compartment of the chemotactic chamber. Different agonists are seeded in the lower compartment of the chamber at the following concentrations: 1 nM CXCL8, 0.03 nM fMLP, 10 nM CXCL1, 2.5 nM CCL2, 30 nM C5a. The chemotactic chamber is incubated at 37°C in air with 5% CO2 for 45 min (human PMNs) or 2 h (monocytes). At the end of incubation, the filter is removed, fixed, and stained and five oil immersion fields at high magnification (100×) are counted for each migration well after sample coding. L1.2 migration is evaluated using 5 μm pore size Transwell filters[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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Animal Administration
[3][4] |
Reparixin is dissolved in saline and administered subcutaneously (Mice and Rat). Rat[3] |
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References |
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Molecular Weight |
283.39 |
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Formula |
C₁₄H₂₁NO₃S |
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CAS No. |
266359-83-5 |
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Storage |
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Shipping | Room temperature in continental US; may vary elsewhere |
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Solvent & Solubility |
DMSO: ≥ 500 mg/mL Reparixin is prepare in vehicle (sterile saline)[5]. * "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">1> |
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References |
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Purity: 99.88% ee.: 100.00%
COA (94 KB) HNMR (178 KB) RP-HPLC (194 KB) NP-HPLC (194 KB) MS (220 KB)
Handling Instructions (1252 KB)-
[1]. Moriconi A, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007 Aug 23;50(17):3984-4002.
[2]. Bertini R, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2non-competitive allosteric inhibitor. Br J Pharmacol. 2012 Jan;165(2):436-54.
[3]. Kim HY, et al. Reparixin, an inhibitor of CXCR1 and CXCR2 receptor activation, attenuates blood pressure and hypertension-related mediators expression in spontaneously hypertensive rats. Biol Pharm Bull. 2011;34(1):120-7.
[4]. Sousa LF, et al. Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice. Clinics (Sao Paulo). 2013;68(3):391-4.
[5]. Krishnamurthy A, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis. 2016 Apr;75(4):721-9.