• 产品描述： 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

• 靶点： RORγt:<30 nM (IC50);ROR

• 体外研究：
  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 CD4+T 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 CD4+T 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.

• 体内研究：
  S18-000003 (30-100 mg/kg; po) 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; iv) 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; po) exhibits the oral bioavailability (54.5%), Cmax (185 ng/mL), AUC (2110 ng•h/mL) and Tmax (4 h) in rats.

• 参考文献：
  1: Sasaki Y, Odan M, Yamamoto S, Kida S, Ueyama A, Shimizu M, Haruna T, Watanabe A, Okuno T. 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. Epub 2018 Sep 27. PubMed PMID: 30301676.
  [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.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	1.928 ml	9.642 ml	19.285 ml
  5 mM	0.386 ml	1.928 ml	3.857 ml
  10 mM	0.193 ml	0.964 ml	1.928 ml
  50 mM	0.039 ml	0.193 ml	0.386 ml

• 注意：部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *