"目录号: HY-15251 ee.: 100.00%
GPCR/G ProteinImmunology/Inflammation-
Reparixin 是一种有效的 CXCL8 受体CXCR1/2变构抑制剂，微弱抑制CXCR2- 调节的细胞迁移 (IC50=100 nM)，但强抑制CXCR1- 调节的细胞趋化 (IC50=1 nM)。
CXCR
相关产品
Plerixafor octahydrochloride-SCH 527123-Reparixin L-lysine salt-Danirixin-SCH 546738-AMD 3465 hexahydrobromide-AMG 487-SB225002-AMD-070 hydrochloride-SCH 563705-NBI-74330-MSX-122-LY2510924-WZ811-IT1t dihydrochloride-
生物活性
Description
Reparixin is a potent inhibitor of both CXCL8 receptorsCXCR1/2, it inhibits weaklyCXCR2-mediated cell migration (IC50=100 nM), whereas it strongly blocksCXCR1-mediated chemotaxis (IC50=1 nM).
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 (IC50values 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].
Clinical Trial
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Ischemia-reperfusion Injury in Liver Transplant-Early Allograft Dysfunction
March 2015
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Metastatic Breast Cancer
June 2015
Phase 2
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Ischemia-Reperfusion Injury-Kidney Diseases
October 2005
Phase 2
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Pancreatectomy for Chronic Pancreatitis
February 2014
Phase 2-Phase 3
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Islet Transplantation in Diabetes Mellitus Type 1,
October 2012
Phase 3
NCT00224406
Dompé Farmaceutici S.p.A
Ischemia-Reperfusion Injury-Lung Transplantation
May 2005
Phase 2
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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].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.