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• 产品描述： GSK805 is a potent, orally bioavailable retinoid-related orphan receptor gamma t (RORγt) inverse agonist that interacts with the receptor's putative ligand binding domain without exerting significant effects on DNA binding

• 靶点： ROR

• 体外研究：
  GSK805 inhibits the expression of IL-17 (at 0.5 µM) in naïve CD4+ T cells activated under Th17-cell-polarizing conditions and affects the broader RORγt-dependent gene network, inhibiting the development and pathogenic function of Th17 cells.

• 体内研究：
  GSK805 significantly reduces the severity of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, when given orally to the hosts at 10 mg/kg daily beginning at the time of disease induction.

• 细胞实验： CD4+CD62LhighCD25 naive CD4+ T cells were purified by FACS sorting following a MACS bead isolation of CD4+ cells. Naive CD4+ cells were activated with plate-bound anti-CD3 (2 μg/ml) and anti-CD28 (2 μg/ml). For Th17 cell differentiation, cultures were supplemented with IL-6 (20 ng/ml) plus TGF-β1 (1 ng/ml), and IL-23 (10 ng/ml) was added after 48 h. RORγt inhibitors or vehicle control DMSO was also included in the cultures. After 96 h, cells were collected for further experiments.

• 动物实验： Animal administration[1]GSK805 are orally administered once daily at 3 doses (1, 3, and 10 mg/kg) to EAE mice from the day of immunization. Compared to the control, the treatment with 9a or 9g resulted in a delay and significant reduction in clinical severity of EAE in a dose-dependent manner. Compared to thiazole ketone amide 2, which only showed EAE efficacy up to day 20 at 100 mg/kg twice daily dosing,32 the biaryl amides 9a and 9g are much more efficacious. This could be attributed to their good in vitro activities as well as much improved oral exposure and CNS penetration. However, it should be noted that although 9g had more brain exposure than 9a, it exhibited less efficacy than 9a in EAE experiments, indicating that there might be additional factors such as "free" brain concentration affecting in vivo efficacy.

• 参考文献：
  1. Xiao S , Yosef N , Yang J , et al. Small-Molecule RORγt Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms[J]. Immunity, 2014, 40(4):477-489. 2. Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors[J]. ACS Medicinal Chemistry Letters:-.

• 溶解性： soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	1.878 ml	9.392 ml	18.784 ml
  5 mM	0.376 ml	1.878 ml	3.757 ml
  10 mM	0.188 ml	0.939 ml	1.878 ml
  50 mM	0.038 ml	0.188 ml	0.376 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。

• 1. [IF=5.6] Shiyuan Jiang et al."Triptolide attenuates CCL4-induced liver fibrosis by regulating the differentiation of CD4+ T cells in mice."INTERNATIONAL IMMUNOPHARMACOLOGY.2023 Dec;125:111206

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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 *