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diABZI STING agonist-1 trihydrochloride
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
diABZI STING agonist-1 trihydrochloride图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
5mg电议
10mg电议
50mg电议
100mg电议

产品介绍
diABZI STING agonist-1 (trihydrochloride) 是干扰素基因 (STING) 受体激动剂的选择性刺激剂,对人和小鼠的 EC50 分别为 130 和 186 nM。

Cell lines

MRC-5 cells

Preparation Method

0.1, 1, 10 μM diABZI, or RDV, or DMSO as a control was added to the basolateral chamber of the ALI, followed by apical challenge with SARS-CoV-2 (Beta CoV/France/IDF0571/2020 strain) challenge apically.The viral RNA collected from apical washes at 48 h and 72 h hpi was quantified, and disruption of the epithelial layer was measured as TEER.

Reaction Conditions

0.1, 1, 10 μM, at 48 h and 72 h

Applications

diABZI in all tested concentration range potently decreased the level of SARS-CoV-2 viral RNA in a dose-dependent manner. Treatment with diABZI at the concentration as low as 0.1 μM fully protected the integrity of the epithelial layer in the ALI model from SARS-CoV-2 challenge.

Animal models

Female C57BL/6Rj mice

Preparation Method

STING agonist diABZI (0.01, 0.1, or 1 μg, i.t.) DMSO (0.25%) vehicle or saline were administered daily in WT mice for 3 consecutive days and parameters were analyzed on day 4. Concentration of CXCL1/KC in the bronchoalveolar lavage fluid (BALF) determined by ELISA.

Dosage form

0.01, 0.1, or 1 μg, i.t.

Applications

Endotracheal administration of diABZI for 3 consecutive days induced a strong airway inflammation within 24 h. CXCL1 was released in the bronchoalveolar space after 0.1–1 μg diABZI administration

产品描述

diABZI STING agonist-1 trihydrochloride, as a STING agonist, is internalized into the cytoplasm through unknown receptor and induce the activation and dimerization of STING followed by TBK1/IRF3 phosporylation leading to type I IFN response.[2]

diABZI STING agonist-1 trihydrochloride can activate STING and has an effictively effect in limiting SARS-CoV-2 replication in cells and animals.[1]

In vitro, diABZI dose dependently protected the cells from CPEs with an EC50 value of 3 nM, suggesting the significant anti-HCoV-229E activity comparable to that of Remdesivir (RDV, EC50 = 26 nM). Furthermore, the half maximal cytotoxic concentration value (CC50) of diABZI was greater than 100 μM in MRC-5 cells, indicating that the observed antiviral effects were not related to nonspecific cytotoxicity.[3]

In vitro, treatment with 0.1 μM diABZI-4 in CD14+ human monocytes it shown that diABZI-4 (STING agonist) induced oligomerization of STING, transcription of IFNB1, TNF, CXCL10 and IL6 and the secretion of TNF-α and IFN-βin primary human CD14+ monocytes. In the meanwhile, 0.1 μM of diABZI-4 also inhibits SARS-CoV-2 replication in lung epithelial cells.[1]In vitro efficacy test, treatment with 1 μM DiABZI induced the release of IFNα, IFNβ, CXCL10, IL-6, TNFα, CXCL1, and IL-10 at 16 h. Treatment with 1–10 μM DiABZI induced the expression of IFNβ, IL-1β, and IL-8. In addition, DiABZI at 0.3–1 μM induced the phosphorylation of STING and downstream TBK1 kinase, together with STAT1 phosphorylation, similar to cGAMP.[2]

In vivo experiment it indicated that after endotracheal administration of 0.1–1 μg diABZI, STING overexpression and activation visible by increased STING dimers in immunoblots of lung tissue.

References:
[1].Humphries F, et al. A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection. Sci Immunol. 2021 May 18;6(59):eabi9002.
[2].Messaoud-Nacer Y, et al. STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS). Cell Death Dis. 2022 Mar 25;13(3):269.
[3].Zhu Q, et al. Inhibition of coronavirus infection by a synthetic STING agonist in primary human airway system. Antiviral Res. 2021 Mar;187:105015.