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Reparixin L-lysine salt
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Reparixin L-lysine salt图片
CAS NO:266359-93-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 429.57
Formula C20H35N3O5S
CAS No. 266359-93-7 (lysine salt);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO:>10 mM
Water: ≥ 200 mg/mL
Ethanol: < 1mg/mL
SMILES N[C@@H](CCCCN)C(O)=O.CS(=O)(NC([C@@H](C1=CC=C(CC(C)C)C=C1)C)=O)=O
Synonyms DF 1681Y L-lysine salt; DF-1681Y L-lysine salt; DF1681Y L-lysine salt; Reparixin; Repertaxin; Repertaxin L-lysine salt
实验参考方法
In Vitro

In vitro activity: Reparixin L-lysine salt, the L-lysine salt form of reparixin, is a novel, potent small molecular weight allosteric inhibitor of chemokine receptor 1/2 (CXCR1/2) activation. It is the first drug candidate currently under clinical investigation in the prevention of ischemia/reperfusion injury in organ transplantation. Reparixin binding mode to CXCR1 has been studied and used for a computer-assisted design program of dual allosteric CXCR1 and CXCR2 inhibitors. Structural and biochemical data are consistent with a noncompetitive allosteric mode of interaction between CXCR1 and Repertaxin, which, by locking CXCR1 in an inactive conformation, prevents signaling. Repertaxin is an effective inhibitor of polymorphonuclear cell recruitment in vivo and protects organs against reperfusion injury. Targeting the Repertaxin interaction site of CXCR1 represents a general strategy to modulate the activity of chemoattractant receptors.


Kinase Assay: Reparixin L-lysine salt, the L-lysine salt form of reparixin, is a novel, potent small molecular weight allosteric inhibitor of chemokine receptor 1/2 (CXCR1/2) activation. 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).


Cell Assay: 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-1 μM) 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.

In VivoThe 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, Vss is 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)
Animal model Male and female Sprague-Dawley CD (albino) rats and male Lister Hooded (partially pigmented) rats are used. Male and female beagle Dogs
Formulation & Dosage Dissolved in sterile isotonic (0.9%, w/v) saline; Rats are dosed with a solution of total drug concentration 9 mg/mL at a dose volume of 5 mL/kg (30 mg free Reparixin /kg) by bolus injection into a caudal vein. Dogs are dosed with a solution of total drug concentration 100 mg/mL at a dose volume of 0.5 mL/kg (33 mg free Reparixin/kg) by bolus injection into a superficial forelimb vein.
References Xenobiotica. 2006 May;36(5):419-40.