diABZI STING agonist-1 trihydrochloride
(Synonyms: Diamidobenzimidazole STING Agonist-1, STING Agonist (Compound 3), STING Agonist diABZI) 目录号 : GC35855diABZI STING agonist-1 trihydrochloride 作为一种 STING 激动剂，通过未知受体内化到细胞质中并诱导 STING 的激活和二聚化，然后是 TBK1/IRF3 磷酸化，从而导致 I 型 IFN 反应。
Cas No.:2138299-34-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
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.
diABZI STING agonist-1 trihydrochloride 作为一种 STING 激动剂，通过未知受体内化到细胞质中并诱导 STING 的激活和二聚化，然后是 TBK1/IRF3 磷酸化，从而导致 I 型 IFN 反应。[2]
diABZI STING agonist-1 trihydrochloride 可激活 STING，并有效限制 SARS-CoV-2 在细胞和动物中的复制。[1]
在体外，diABZI 剂量依赖性地保护细胞免受 CPE 的影响，EC50 值为 3 nM，这表明其显着的抗 HCoV-229E 活性可与 Remdesivir（RDV，EC50 = 26 nM）相媲美。此外，diABZI 在 MRC-5 细胞中的半数最大细胞毒性浓度值 (CC50) 大于 100 μM，表明观察到的抗病毒作用与非特异性细胞毒性无关。[3]
在体外，用 0.1 μM diABZI-4 处理 CD14+ 人单核细胞表明 diABZI-4（STING 激动剂）诱导 STING 的寡聚化、IFNB1、TNF、CXCL10 和 IL6 的转录以及 TNF-α 和 IFN 的分泌-β 在原代人 CD14+ 单核细胞中。同时，0.1 μM 的 diABZI-4 也抑制 SARS-CoV-2 在肺上皮细胞中的复制。 [1] 体外药效试验，1μM DiABZI 处理在 16h 诱导 IFNα、IFNβ、CXCL10、IL-6、TNFα、CXCL1 和 IL-10 的释放。用 1-10μM DiABZI 处理可诱导 IFNβ、IL-1β 和 IL-8 的表达。此外，0.3-1μM 的 DiABZI 诱导 STING 和下游 TBK1 激酶的磷酸化，以及 STAT1 磷酸化，类似于 cGAMP。[2]
体内实验表明，气管内给予 0.1-1μg diABZI 后，肺组织免疫印迹中 STING 二聚体增加可见 STING 过表达和激活。
| Cell experiment [1]: | |
|
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 experiment [2]: | |
|
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 |
|
References: [1].Zhu Q, et al. Inhibition of coronavirus infection by a synthetic STING agonist in primary human airway system. Antiviral Res. 2021 Mar;187:105015. [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. |
|
| Cas No. | 2138299-34-8 | SDF | |
| 别名 | Diamidobenzimidazole STING Agonist-1, STING Agonist (Compound 3), STING Agonist diABZI | ||
| Canonical SMILES | O=C(N)C1=CC(N=C(NC(C2=CC(C)=NN2CC)=O)N3C/C=C/CN4C(NC(C5=CC(C)=NN5CC)=O)=NC6=C4C(OCCCN7CCOCC7)=CC(C(N)=O)=C6)=C3C(OC)=C1.Cl.Cl.Cl | ||
| 分子式 | C42H54Cl3N13O7 | 分子量 | 959.32 |
| 溶解度 | DMSO: 125 mg/mL (130.30 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.0424 mL | 5.212 mL | 10.4241 mL |
| 5 mM | 0.2085 mL | 1.0424 mL | 2.0848 mL |
| 10 mM | 0.1042 mL | 0.5212 mL | 1.0424 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet