S18-000003

2068119-11-7

518.55

10 mM in DMSO

Metabolic Enzyme/Protease

S18-000003 is a potent, selective and orally active inhibitor of retinoic acid receptor-related orphan receptor-gamma-t (RORgammat), with an IC50 of <30 nM towards human RORgammat in competitive binding assays. S18-000003 shows selectivity for RORgammat over other ROR family members (IC50s>10 uM). S18-000003 can be used for the research of psoriasis with low risk of thymic aberrations.
In Vitro: S18-000003 inhibits human and mouse RORgammat-dependent transactivation, with IC50s of 0.029 and 0.34 uM respectively in cell-based GAL4 promoter reporter assays.

S18-000003 (0.003-0.3 uM; 7 d) dose-dependently inhibits Th17 cell differentiation from human naive CD4+T cells, with an IC50 of 0.024 uM.

S18-000003 (0.1-3 uM; 4 d) inhibits the differentiation of mouse Th17 cells from splenic naive CD4+T cells, with an IC50 of 0.20 uM.

S18-000003 (0.03-1 uM; 3 d) reduces the IL-17 production in human PBMCs in a dose-dependent manner, and does not inhibit either the production of other cytokines (IL-2, IL-4, IL-10 and IFN-g) or cell proliferation.

S18-000003 (0.1-3 uM; 3 d) reduces IL-17 and IL-22 production in PBMCs from psoriatic mice in a dose-dependent manner.
In Vivo: S18-000003 (30-100 mg/kg; p.o.) inhibits IL-17 production in the skin of IL-23-treated mice in a dose-dependent manner.

S18-000003 (0.1-8%; 100mL; topically administration once daily for 14 days) ameliorates psoriasis-like lesions in TPA-induced K14.Stat3C transgenic mice, and has little impact on the thymus.

S18-000003 (0.5 mg/kg; i.v.) exhibits the half-life (3.2 h), AUC (1930 ng?h/mL), CLtot (4.33 mL/min/kg) and Vdss in rats.

S18-000003 (1 mg/kg; p.o.) exhibits the oral bioavailability (54.5%), Cmax (185 ng/mL), AUC (2110 ng?h/mL) and Tmax (4 h) in rats.