Uses
S18-000003 is a potent, selective and orally active inhibitor of retinoic acid receptor-related orphan receptor-gamma-t (RORγt), with an IC50 of <30 nM towards human RORγt in competitive binding assays. S18-000003 shows selectivity for RORγt over other ROR family members (IC50>10 μM). S18-000003 can be used for the research of psoriasis with low risk of thymic aberrations[1][2].
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[1].
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[2].
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[1].
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[1].
References
[1] Sasaki Y, et, al. Discovery of a potent orally bioavailable retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitor, S18-000003. Bioorg Med Chem Lett. 2018 Dec 1;28(22):3549-3553. DOI:
10.1016/j.bmcl.2018.09.032[2] Imura C, et, al. A novel RORγt inhibitor is a potential therapeutic agent for the topical treatment of psoriasis with low risk of thymic aberrations. J Dermatol Sci. 2019 Mar;93(3):176-185. DOI:
10.1016/j.jdermsci.2019.03.002
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