Stimulator of interferon genes (STING), an integral ER-membrane protein, is a protein that in humans is encoded by the STING1 gene. STING plays an important role in innate immunity. It activates interferon (IFN) and inflammatory cytokine responses to defend against infection by microorganisms. Moreover, the STING signaling pathway is also a critical link between innate and adaptive immunity and induces anti-tumor immune responses. For instance, STING induces type I interferon production when cells are infected with intracellular pathogens, such as viruses, mycobacteria, and intracellular parasites. STING agonists, like endogenous cyclic dinucleotide (CDN) cyclic GMP-AMP (cGAMP), have the potential for various studies in immunogenic tumor clearance, antiviral therapy, and vaccine adjuvants. Therefore, it is very necessary to develop more STING agonists for tumor immunotherapy.
TAK-676 is a STING agonist, triggering the activation of the STING signaling pathway and type I interferons.
Also, TAK-676 is a highly potent modulator of both the innate and adaptive immune systems. This compound promotes the activation of dendritic cells, natural killer cells, and T cells in preclinical models. Furthermore, TAK-676 promotes durable IFN-dependent antitumor immunity. For example, in syngeneic murine tumor models, TAK-676 induces dose-dependent cytokine responses and increases the activation and proliferation of immune cells within the tumor microenvironment (TME) and tumor-associated lymphoid tissue. In vivo, TAK-676 shows STING-dependent antitumor activity, including complete regressions and durable memory T-cell immunity. Besides, TAK-676 exhibits dose-proportional pharmacokinetics in plasma and exhibits higher exposure in tumors. Thus, the intravenous administration of TAK-676 offers potential therapeutic benefits in a broad range of tumor types.
To sum up, TAK-676 is a STING agonist promoting durable IFN-dependent antitumor immunity in preclinical studies.
 Elizabeth Carideo Cunniff, et al. Cancer Research Communications (2022) 2 (6): 489-502.