GSK805

CAS号

1426802-50-7

分子式

C23H18Cl2F3NO4S

主要靶点

ROR

仅限科研使用

Cat No : CM06346

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Synonyms

CNS penetrant|immunity|inhibit|GSK-805|GSK805|GSK 805|oral|RAR-related orphan receptor|Inhibitor|Th17 cell|RORγt|ROR



产品信息

CAS号 1426802-50-7
分子式 C23H18Cl2F3NO4S
主要靶点 ROR
主要通路 代谢
分子量 532.36
纯度 98.23%, 此纯度可做参考,具体纯度与批次有关系,可咨询客服
储存条件 Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
别名 CNS penetrant|immunity|inhibit|GSK-805|GSK805|GSK 805|oral|RAR-related orphan receptor|Inhibitor|Th17 cell|RORγt|ROR

体内活性

方法: 诱导 C57BL/6 小鼠进行 EAE 并用 GSK805 (30 mg/kg,口服,14天) 处理。分离中枢神经系统浸润细胞,并通过细胞内染色测量 IL-17 和 IFNγ 的产生。 结果: GSK805 强烈抑制 CNS 中的 Th17 细胞反应(减少 IFNγIL-17 和 IFNγIL-17 T 细胞),而 TNF-α T 细胞的频率没有显着改变)。[1] 方法: GSK805(1、3 和 10 mg/kg,口服,每天三次)给 EAE 小鼠 ,观察其对小鼠的影响。 结果: GSK805能以以剂量依赖性方式降低 EAE 的临床严重程度。[2]

体外活性

方法: GSK805 (0.5 μM,4天)处理CD4 T 细胞(在 Th17 细胞分化条件下激活)。通过细胞内细胞因子染色测量 IL-17 和 IFNγ 的产生。 结果: GSK805 在Th17 细胞分化状态下产生了抑制作用。[1]

溶解度

DMSO:100 mg/mL (187.84 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:10 mg/mL (18.78 mM)

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[1].

参考文献

1.Xiao S, et al. Small-molecule RORγt antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms. Immunity. 2014 Apr 17;40(4):477-89.
2.Wang Y, et al. Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors. ACS Med Chem Lett. 2015 May 26;6(7):787-92.

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