| Description |
TAK-676 is an agonist of STING, triggering the activation of STING signaling pathway and type 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].
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| Related Catalog |
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| Target |
STING, Type I interferons[1]
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| 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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| 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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| References |
[1]. Elizabeth CC, et al. TAK-676: A Novel Stimulator of Interferon Genes (STING) Agonist Promoting Durable IFN-dependent Antitumor Immunity in Preclinical Studies. Cancer Research Communications. 2022. 2(6): 489–502.
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