Reparixin-(Repertaxin)-CXCR-Inhibitor-MedChemExpress

Reparixin

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].

体内研究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].

PROTOCOL

Cell Assay [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.

Animal Administration [3][4]Rats[3]

The Reparixin-treated group contained 5 SHR (SHR-R), where equal numbers of normal saline-treated SHR (SHR-N) and WKY (WKY-N) served as controls. Eighteen-week-old SHR received a subcutaneous injection of Reparixin (5

mg/kg) once per day for 3 weeks. Reparixin effects on blood flow, blood pressure and body weight are measured before treatment and then weekly until 1 week after the final injection. The effect of Reparixin on the expression of hypertension-related mediators in thoracic aortas, as well as nitric oxide (NO) plasma levels, is examined 1 week after the final injection. At the end of the 4 week period, both control and Reparixin-treated rats are anesthetized via intraperitoneal injection of thiopental (50 mg/kg), and blood and tissue samples are collected.

Mice[4]

C57BL/6J mice (8-10 weeks old/20-25 g) are used. The subcutaneous administration of Reparixin (30 mg/kg) is performed 60 minutes before cerebral ischemia induction. The animals are divided into the following three experimental groups: Sham (i.e., the group in which the arteries are visualized, but there is no occlusion of the middle cerebral artery), Vehicle (i.e., the group pre-treated with the vehicle, phosphate buffer solution, 60 minutes before MCAo) and Reparixin (i.e., the group pre-treated with the drug 60 minutes before MCAo). To evaluate neurological signs secondary to MCAo, the animals are assessed with the SHIRPA battery 24 h after reperfusion.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

客户使?本产品发表的科研?献

? J Allergy Clin Immunol. 2018 Jun;141(6):2286-2289.e5.? Nat Commun. 2017 May 26;8:15584.

? Ann Rheum Dis. 2016 Apr;75(4):730-8.

? Ann Rheum Dis. 2016 Apr;75(4):721-9.

? Sci Adv. 2019 May 8;5(5):eaav7384.

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REFERENCES

[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]. Bertini R, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11791-6.

[6]. 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.

[7]. Crespo J, et al. Human Naive T Cells Express Functional CXCL8 and Promote Tumorigenesis. J Immunol. 2018 Jul 15;201(2):814-820.

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Caution: Product has not been fully validated for medical applications. For research use only.

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