SB 332235

SB-332235 is a potent, orally active nonpeptide CXCR2 antagonist, with an IC50 of 7.7 nM. SB-332235 displays 285-fold selectivity for CXCR2 over CXCR1. SB-332235 inhibits acute and chronic models of arthritis in the rabbit. SB-332235 inhibits viability of AML cells[1][2].

Signaling Pathways >> GPCR/G Protein >> CXCR

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Immunology/Inflammation >> CXCR

SB-332235 (1-100 μM; 48 hours) inhibits viability of AML cell lines[2]. Cell Viability Assay[2] Cell Line: AML cell Concentration: 1, 10, 100 μM Incubation Time: 48 hours Result: Led to a dose-dependent decrease in proliferation in all cell lines.

SB-332235 (25 mg/kg, p.o., b.i.d.) exhibits significantly reduced numbers of total leukocytes in synovial fluids from IL-8-injected knees[1]. SB-332235 (10-25 mg/kg; p.o.; twice a day for 14 days) inhibits chronic Ag-induced arthritis[1]. Animal Model: Adult female New Zealand White rabbits (chronic OVA-induced model of arthritis)[1] Dosage: 10, 25 mg/kg Administration: P.o.; twice a day for 14 days Result: Day-15 synovial fluid leukocyte numbers in OVA-injected knees were significantly reduced in rabbits. The decrease in neutrophils, monocytes, and lymphocytes resulting from treatment with 25 mg/kg of the antagonist was accompanied by a significant reduction in synovial fluid PGE2, LTB4, LTC4, and IL-8 levels.

[1]. Podolin PL, et al. A potent and selective nonpeptide antagonist of CXCR2 inhibits acute and chronic models of arthritis in the rabbit. J Immunol. 2002;169(11):6435-6444.

[2]. Schinke C, et al. IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells [published correction appears in Blood. 2015 Jul 16;126(3):425. Barreryo, Laura [corrected to Barreyro, Laura]]. Blood. 2015;125(20):3144-3152.