CXCR1 Antagonist

Navarixin (SCH 527123) is a potent, allosteric and orally active antagonist of both CXCR1 and CXCR2, with K_d values of 41 nM for cynomolgus CXCR1 and 0.20 nM, 0.20 nM, 0.08 nM for mouse, rat and cynomolgus monkey CXCR2, respectivelly.

SX-517 is a dual CXCR2/1 antagonist, containing boronic acid. SX-517 inhibits CXCL1-induced Ca²⁺ flux (IC₅₀=38 nM), and antagonizes CXCL8-induced [(35)S]GTPγS binding (IC₅₀=60 nM) and ERK1/2 phosphorylation. SX-517 has significant ability for inflammation suppression, in both humanized polymorphonuclear (PMN) cells and in murine model.

Ladarixin sodium (DF 2156A) is an orally active, allosteric non-competitive and dual CXCR1 and CXCR2 antagonist. Ladarixin sodium can be used for the research of COPD and asthma.

SCH 563705 is a potent and orally available CXCR2 and CXCR1 antagonist, with IC₅₀s of 1.3 nM, 7.3 nM and K_is of 1 and 3 nM, respectively.

CXCR2-IN-2 is a selective, brain penetrant, and orally bioavailable CXCR2 antagonist (IC₅₀=5.2 nM/1 nM in β-arrestin assay/CXCR2 Tango assay, respectively). CXCR2-IN-2 displays ~730-fold selectivity over CXCR1 and >1900-fold selectivity over all other chemokine receptors. CXCR2-IN-2 inhibits human whole blood Gro-α induced CD11b expression with an IC₅₀ of 0.04 μM.