Reparixin L-lysine salt

"目录号: HY-15252

GPCR/G ProteinImmunology/Inflammation-

Reparixin L-lysine salt 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-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

NCT01220856

Dompé Farmaceutici S.p.A

Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus

July 2010

Phase 2

NCT02001974

Dompé Farmaceutici S.p.A-PRA Health Sciences

Metastatic Breast Cancer

January 2012

Phase 1

NCT01861054

Dompé Farmaceutici S.p.A

Breast Cancer

February 2013

Phase 2

NCT03031470

Dompé Farmaceutici S.p.A

Ischemia-reperfusion Injury in Liver Transplant-Early Allograft Dysfunction

March 2015

Phase 2

NCT02370238

Dompé Farmaceutici S.p.A-PRA Health Sciences

Metastatic Breast Cancer

June 2015

Phase 2

NCT00248040

Dompé Farmaceutici S.p.A

Ischemia-Reperfusion Injury-Kidney Diseases

October 2005

Phase 2

NCT01967888

Dompé Farmaceutici S.p.A

Pancreatectomy for Chronic Pancreatitis

February 2014

Phase 2-Phase 3

NCT01817959

Dompé Farmaceutici S.p.A

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].Midgley I, et al. Species differences in the pharmacokinetics and metabolism of reparixin in rat and dog. Xenobiotica. 2006 May;36(5):419-40.

[4].Catrina, Anca, et al. METHODS AND COMPOUNDS FOR THE TREATMENT OF BONE LOSS AND/OR PAIN. US 20170105971 A1.