S18-000003 是一种有效，选择性和具有口服活性的维甲酸相关孤儿受体 (RORγt) 的抑制剂，在竞争性结合试验中，对 hRORγt 的 IC₅₀ 值小于 30 nM。S18-000003 对于 RORγt 的选择性高于其他 ROR 家族成员 (IC₅₀>10 μM)。S18-000003 可用于研究银屑病，并且具有较低的胸腺畸变风险。

S18-000003 is a potent, selective and orally active inhibitor of retinoic acid receptor-related orphan receptor-gamma-t (RORγt), with an IC 50 of <30 nM towards human RORγt in competitive binding assays. S18-000003 shows selectivity for RORγt over other ROR family members (IC 50 >10 μM). S18-000003 can be used for the research of psoriasis with low risk of thymic aberrations.

Solid

RORγt <30 nM (IC50)

S18-000003 inhibits human and mouse RORγt-dependent transactivation, with IC50s of 0.029 and 0.34 μM respectively in cell-based GAL4 promoter reporter assays.
S18-000003 (0.003-0.3 μM; 7 d) dose-dependently inhibits Th17 cell differentiation from human naive CD4T cells, with an IC50 of 0.024 μM.
S18-000003 (0.1-3 μM; 4 d) inhibits the differentiation of mouse Th17 cells from splenic naive CD4T cells, with an IC50 of 0.20 μM.
S18-000003 (0.03-1 μM; 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 μM; 3 d) reduces IL-17 and IL-22 production in PBMCs from psoriatic mice in a dose-dependent manner. has not independen

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), CL tot (4.33 mL/min/kg) and Vd ss in rats.
S18-000003 (1 mg/kg; p.o.) exhibits the oral bioavailability (54.5%), C max (185 ng/mL), AUC (2110 ng?h/mL) and T max (4 h) in rats. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；In solvent -80°C 6 months

[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.
[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.

In Vitro: DMSO : 100 mg/mL (192.85 mM; Need ultrasonic)配制储备液