"目錄號: HY-15252
GPCR/G ProteinImmunology/Inflammation-
Reparixin L-lysine salt 是一種有效的 CXCL8 受體CXCR1/2變構抑制劑请梢，微弱抑制CXCR2- 調(diào)節(jié)的細胞遷移 (IC50=100 nM)，但強抑制CXCR1- 調(diào)節(jié)的細胞趨化 (IC50=1 nM)椒拗。
相關產(chǎn)品
Plerixafor octahydrochloride-Reparixin-SCH 527123-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 L-lysine salt is a potent and specific allosteric 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
The pharmacokinetics and metabolism of Reparixin are investigated in rats and dogs after intravenous administration of [14C]-Reparixin L-lysine salt. Plasma protein binding of Reparixin is >99% in the laboratory animals and humans up to 50 μg/mL, but lower at higher concentrations. Although radioactivity is rapidly distributed into rat tissues, Vssis low (about 0.15 L/kg) in both rat and dog. Nevertheless, Reparixin is more rapidly eliminated in rats (t1/2~0.5 h) than in dogs (t1/2~10 h)[3].
Clinical Trial
Dompé Farmaceutici S.p.A
Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus
July 2010
Phase 2
Dompé Farmaceutici S.p.A-PRA Health Sciences
Metastatic Breast Cancer
January 2012
Phase 1
Dompé Farmaceutici S.p.A
Breast Cancer
February 2013
Phase 2
Dompé Farmaceutici S.p.A
Ischemia-reperfusion Injury in Liver Transplant-Early Allograft Dysfunction
March 2015
Phase 2
Dompé Farmaceutici S.p.A-PRA Health Sciences
Metastatic Breast Cancer
June 2015
Phase 2
Dompé Farmaceutici S.p.A
Ischemia-Reperfusion Injury-Kidney Diseases
October 2005
Phase 2
Dompé Farmaceutici S.p.A
Pancreatectomy for Chronic Pancreatitis
February 2014
Phase 2-Phase 3
Dompé Farmaceutici S.p.A
Islet Transplantation in Diabetes Mellitus Type 1,
October 2012
Phase 3
Dompé Farmaceutici S.p.A
Ischemia-Reperfusion Injury-Lung Transplantation
May 2005
Phase 2
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References
