Reparixin L-lysine salt

• CAT Number: I002913
• CAS Number: 266359-93-7
• Molecular Formula: C20H35N3O5S
• Molecular Weight: 429.57
• Purity: ≥95%
• Synonyms: (2S)-2,6-diaminohexanoic acid;(2R)-2-[4-(2-methylpropyl)phenyl]-N-methylsulfonylpropanamide
• InChI: InChI=1S/C14H21NO3S.C6H14N2O2/c1-10(2)9-12-5-7-13(8-6-12)11(3)14(16)15-19(4,17)18;7-4-2-1-3-5(8)6(9)10/h5-8,10-11H,9H2,1-4H3,(H,15,16);5H,1-4,7-8H2,(H,9,10)/t11-;5-/m10/s1
• InChIKey: JEJFWWFZAQBZMJ-GVKMLHTLSA-N
• SMILES: CC(C)CC1=CC=C(C=C1)C(C)C(=O)NS(=O)(=O)C.C(CCN)CC(C(=O)O)N

Reparixin L-lysine salt is an 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)[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].
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, 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)[3].

Reference

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

[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.
 [Content Brief]