TAK-676 是一种干扰素基因刺激因子激动剂 (STING)，触发STING信号通路激活和 I 型干扰素激活。TAK-676 也是一种免疫系统调节剂，具有完全消退和持久记忆的 T 细胞免疫功能。TAK-676 能够促进持久的干扰素依赖性抗肿瘤免疫反应。
| 生物活性 | TAK-676 is an agonist ofSTING, triggering the activation ofSTINGsignaling pathway andtype I interferons. TAK-676 is also a modulator of immune system, resulting complete regressions and durable memory T-cell immunity. TAK-676 promotes durable IFN-dependent antitumor immunity[1]. |
| IC50& Target | STING, Type I interferons[1] |
体外研究
(In Vitro) | TAK-676 (1.1, 3.3, and 10 μM; 2 h) dose-dependently activates the STING-TBK1-IRF3 pathway in THP1-Dual human AML cells and CT26.WT cells, but is critically dependent on STING expression[1].
TAK-676 (0-1 μM; 24 h) exerts in vitro immune cell activation function in mouse BM-derived dendritic cells in a dose-dependent manner[1].
TAK-676 (0-1 μM; 24 h) promotes the activation of dendritic cells (DC), natural killer (NK) cells, and T cells, with activation EC50s of 1.27 μM (MoDC), 0.32 μM (BMDC), 0.271 μM (NK), 0.216 μM (CD8+), 0.249 μM (CD4+) at 24 h, respectively[1].
Western Blot Analysis[1] | Cell Line: | THP1-Dual human AML cells and CT26.WT cells | | Concentration: | 1.1, 3.3, 10 μM | | Incubation Time: | 2 hours | | Result: | Increased pTBK1, pSTING, pIRF3 protein level in a dose-dependent manner.
Not induced the phosphorylation of pTBK1 (S172) or pIRF3 (S396) in the absence of STING expression. |
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体内研究
(In Vivo) | TAK-676 (0.025-2 mg/kg; i.v.; single dose) is well tolerated, exhibits dose-proportional pharmacokinetics in plasma, and exhibits higher exposure in tumor in mice[1].
TAK-676 (1 mg/kg/d, 2 mg/kg/d; i.v.; 13 d) shows anti-tumor function on BALB/c mice bearing A20 syngeneic tumors/CT26.WT syngeneic tumors mode[1].
| Animal Model: | BALB/c mice bearing A20 syngeneic tumors/CT26.WT syngeneic tumors model[1] | | Dosage: | 1 or 2 mg/kg/day | | Administration: | Intravenous injection; for 3, 6, 9, 12 day, respectively | | Result: | Resulted in significant T cell–dependent in vivo antitumor activity.
Induced dose-dependent cytokine responses and increased the activation and proliferation of immune cells within the TME and tumor-associated lymphoid tissue. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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