diABZI STING agonist-1 trihydrochloride

diABZI STING agonist-1 trihydrochloride is a potent non-nucleotide small molecule STING receptor agonist (EC₅₀=130nM, 186nM). diABZI STING agonist-1 trihydrochloride binds and activates endoplasmic reticulum-localized STING protein, stabilizes its open conformation, recruits and activates TBK1, promotes IRF3 phosphorylation and nuclear translocation, and induces type I interferon and multiple pro-inflammatory cytokines and chemokines expression. diABZI STING agonist-1 trihydrochloride can be used in tumor immunotherapy, antiviral and infectious disease research, and cGAS-STING innate immune signaling pathway studies^[1-4].

In vitro, treatment of bone marrow monocytes (BMMs) with 10-200nM diABZI STING agonist-1 trihydrochloride for 6 days reduced the number and area of TRAP-positive multinucleated cells and decreased bone resorption pit area^[5]. Treatment of A549 and H1975 cells with 20nM diABZI STING agonist-1 trihydrochloride for 3-14 days upregulated p-STING, cGAS, p-TBK1 and p-IRF3 protein expression, increased IFNβ, CCL5 and CXCL10 mRNA expression and corresponding protein secretion in culture supernatant, with effects similar to ESYT3 overexpression^[6]. Treatment of 1G4 HA-TCR engineered T cells with 0.5-10μg/mL diABZI STING agonist-1 trihydrochloride for 3 hours enhanced T cell killing activity against Mel526 and NY-ESO-1 knockout Mel526 cells and increased IFNγ expression^[7].

In vivo, a single subcutaneous injection of 2.5mg/kg diABZI STING agonist-1 trihydrochloride into the shaved back region of female BALB/cJ mice induced erythema on day 3, desquamation on day 4, and induration on day 9, along with epidermal thickening, hyperkeratosis, dermal inflammation and fibrosis, ulceration, and neutrophil infiltration^[8]. Intratracheal instillation of 0.01-1μg diABZI STING agonist-1 trihydrochloride (40μL) into C57BL/6Rj mice for 3 consecutive days triggered acute neutrophilic airway inflammation, disrupted respiratory barrier function, induced CXCL1 release, neutrophil recruitment, MPO elevation, and total protein exudation in BALF^[9]. On days 9 and 13 after tumor implantation, intracranial administration of 0.25mg/kg diABZI STING agonist-1 trihydrochloride via an implanted catheter into C57BL/6 mice bearing CT-2A intracerebral tumors, combined with 3Gy×3 local radiotherapy on days 7, 8, and 9, suppressed tumor growth and prolonged mouse survival^[10].

References:

[1] Ramanjulu JM, Pesiridis GS, Yang J, et al. Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature. 2018 Dec;564(7736):439-443.

[2] 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.

[3] Xu Z, Ma Z, Ren H, et al. Exercise training ameliorates high-fat diet-induced skeletal muscle atrophy and ferroptosis via downregulation of STING. Free Radic Biol Med. 2025 Dec 1;240:373-383.

[4] Linder A, Nixdorf D, Kuhl N, et al. STING activation improves T-cell-engaging immunotherapy for acute myeloid leukemia. Blood. 2025 May 8;145(19):2149-2160.

[5] Huang Y, Zhang M, Zhang J, et al. diABZI and poly(l:C) inhibit osteoclastic bone resorption by inducing IRF7 and IFIT3. Journal of Bone and Mineral Research. 2024 Aug;39(8):1132-1146.

[6] Luo Z, Li Y, Xu B, et al. Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma. Experimental Hematology & Oncology. 2024 Aug 5;13:77.

[7] Wang L, Liang Z, Guo Y, et al. STING agonist diABZI enhances the cytotoxicity of T cell towards cancer cells. Cell Death and Disease. 2024 Apr 13;15:265.

[8] Pyclik M, Durslewicz J, Papinska JA, et al. STING Agonist-Induced Skin Inflammation Is Exacerbated with Prior Systemic Innate Immune Activation. International Journal of Molecular Sciences. 2023 Feb 18;24(4):4128.

[9] Messaoud-Nacer Y, Culerier E, Rose S, et al. STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome(ARDS). Cell Death and Disease. 2022 Mar 25;13:269.

[10] Zhang P, Rashidi A, Zhao J, et al. STING agonist-loaded, CD47/PD-L1-targeting nanoparticles potentiate antitumor immunity and radiotherapy for glioblastoma. Nature Communications. 2023 Mar 23;14:1610.