diABZI STING agonist-1 (Tautomerism) is a potent and selective stimulator of interferon genes (STING) receptor agonist. diABZI STING agonist-1 (Tautomerism) activates human (EC50=130nM) or mouse (EC50=186nM) STING. diABZI STING agonist-1 (Tautomerism) induces type I IFN response via TBK1/IRF3 phosphorylation. diABZI STING agonist-1 (Tautomerism) promotes TNF, IL-6, CXCL10 expression via NF-κB related pathways. diABZI STING agonist-1 (Tautomerism) can be used in tumor immunity, SARS-CoV-2 antiviral research, innate immunity, and coronavirus infection research[1-4].
In vitro, 3µM diABZI STING agonist-1 (Tautomerism) treated human peripheral blood mononuclear cells for 4h. diABZI STING agonist-1 (Tautomerism) induced STING and IRF3 phosphorylation, induced IFNβ, IP-10, IL-6, and TNF secretion[5]. 5μM diABZI STING agonist-1 (Tautomerism) stimulated THP-1 cells and RAW 264.7 cells for 30s to 24h. diABZI STING agonist-1 (Tautomerism) activated cGAS-STING signaling pathway, induced STING, IRF3, TBK1, and NF-κB phosphorylation[6].
In vivo, BALB/c mice with 4T1 tumor xenografts received 1.5mg/kg diABZI STING agonist-1 (Tautomerism) via tail vein injection three times per week for 14 days. diABZI STING agonist-1 (Tautomerism) inhibited tumor growth, increased CD3+ and CD8+ T cell infiltration in tumors[7]. MDA-MB-231 xenograft NSG mice received 1.5mg/kg diABZI STING agonist-1 (Tautomerism) combined with 10mg/kg ABT-737 via tail vein injection twice per week for 9 weeks. diABZI STING agonist-1 (Tautomerism) slowed tumor growth[8]. Chronic HBV replication C57BL/6J mouse model received single intraperitoneal injection of 1.5mg/kg diABZI STING agonist-1 (Tautomerism) and 360mg/kg Acetaminophen. At 6h after injection, diABZI STING agonist-1 (Tautomerism) activated STING, TBK1, IRF3 phosphorylation, up-regulated LC3B and down-regulated p62 to induce autophagy, increased hepatocyte p-STAT3, decreased IL-1β, INOS, CXCL16 expression, decreased serum ALT, AST, ALP, NLR, increased peripheral blood monocytes, decreased TUNEL positive cells, alleviated liver inflammation and injury. At 24h and 48h after injection, diABZI STING agonist-1 (Tautomerism) promoted liver macrophage polarization to M1 phenotype, increased serum ALT, AST, TBA, ALP, NLR, decreased peripheral blood monocytes, increased TUNEL positive cells. At 48h, diABZI STING agonist-1 (Tautomerism) aggravated liver inflammation and injury[9].
References:[1] Pyclik M, Durslewicz J, Papinska JA, et al. STING Agonist-Induced Skin Inflammation Is Exacerbated with Prior Systemic Innate Immune Activation. Int J Mol Sci. 2023 Feb 18;24(4):4128.
[2] Garland KM, Sheehy TL, Wilson JT. Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy. Chem Rev. 2022 Mar 23;122(6):5977-6039.
[3] Wang L, Liang Z, Guo Y, et al. STING agonist diABZI enhances the cytotoxicity of T cell towards cancer cells. Cell Death Dis. 2024 Apr 13;15(4):265.
[4] Li Y, Chen W, Zhang X, et al. STING agonist diABZI confers protection against swine acute diarrhea syndrome coronavirus in neonatal mice by activating antiviral immunity. J Virol. 2026 Feb 17;100(2):e0170325.
[5] Ramanjulu JM, Pesiridis GS, Yang J, et al. Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature. 2018 Nov;563(7730):223-227.
[6] Zhang Z, Wei X, Huang Q, et al. Discovery of STING antagonists targeting cGAS-STING pathway to alleviate IMQ-induced psoriasis-like dermatitis. Eur J Pharm Sci. 2025;210:107091.
[7] Gao Y, Zheng X, Chang B, et al. Intercellular transfer of activated STING triggered by RAB22A-mediated non-canonical autophagy promotes antitumor immunity. Cell Res. 2022;32(12):1086-1104.
[8] Lohard S, Bourgeois N, Maillet L, et al. STING-dependent paracriny shapes apoptotic priming of breast tumors in response to anti-mitotic treatment. Nat Commun. 2020;11:259.
[9] Zhang H, Liang T, Duan W, et al. STING modulates HBV-related acute-on-chronic liver failure by mediating autophagy and macrophage polarization. Immunobiology. 2025;230:152860.