AbMole C-176 是一种有效的具有选择性和血脑屏障渗透性的 STING抑制剂。STING是细胞内DNA感应通路的主要信号分子。C-176 可共价靶向跨膜半胱氨酸残基 91，从而阻断激活诱导的 STING 棕榈酰化。C-176 可以抑制破骨细胞前体细胞中的STING活化，并以剂量依赖的方式，抑制NF-κB配体的受体激活剂诱导的破骨细胞活化，具有抗炎活性。
C-176 strongly reduces STING-mediated, but not RIG-I- or TBK1-mediated, IFNβ reporter activity. Pretreatment with C-176 markedly reduce the CMA-mediated induction of serum levels of type I IFNs and IL-6.
C-176 (750/375 nmol C-176 per mouse in 200 μL corn oil) significantly reduces the CMA-mediated induction of serum levels of type I IFNs and IL-6, without significant toxicity.
C-176 results in a significant reduction in serum levels of type I IFNs and in a strong suppression of inflammatory parameters in the heart, with no evident signs of overt toxicity Trex1−/− mice.
C-176 demonstrates marked amelioration of various signs of systemic inflammation in Trex1−/− mice.
实验参考（摘自公开文献，AbMole尚未独立证实这些方法的准确性）
BV2 cells were cultured in Dulbecco's modified eagle medium (DMEM) containing 5% foetal bovine serum (FBS) and 1% penicillin–streptomycin at 37°C/5% CO2. Cells were plated in a six-well plate at a density of 1 × 106 cells per well. Cells were pre-treated for 30 min in media containing 0.1- to 2-μM C-176 or a DMSO vehicle. Following pre-treatment, cyclic di-GMP (c-di-GMP) was added to a final well concentration of 10–20 μg/ml for 8 h. Control wells were treated with an equivalent volume of endotoxin-free water. Following treatments, culture medium was removed and wells were gently rinsed twice with ice cold phosphate-buffered saline (PBS). Cells were scraped in PBS using a handheld cell scraper and placed in a cold Eppendorf tube. Samples were centrifuged at 3000g at 4°C for 10 min. Supernatants were removed and cell pellets stored at −80°C until required.
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16347
Mice were randomly assigned to receive either a sham or mild controlled cortical impact surgery (TBI). Thirty minutes following impact, a 200-μL intravenous tail vein injection of 750-nmol C-176 diluted in phosphate-buffered saline (PBS) or a PBS vehicle was administered. Blinding of both the operator and data analysis was conducted by concealing the identity of the solution administered to mice post-TBI. Magnetic resonance imaging (MRI) measuring lesion size was performed 24 h and 7 days after TBI. DigiGait analysis measuring behavioural outcome was conducted 24 h after TBI and biochemical analysis was conducted 2 h and 24 h after TBI. In this study, the identity of each animal with respect to treatment was blinded to researchers who conducted the experiments and analysis.
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16347
MCD diet-induced NASH model
The study included feeding 6-week-old female C57BL/6 mice with either a methionine-choline-deficient or a methionine-choline-sufficient diet for 6 weeks. The model group was given the MCD diet, whereas the control group was given the MCS diet. At the same time, the treatment group received licorice extract dissolved in physiological saline (500 mg/kg to make a solution of 2 mg/mL, and no precipitation was observed) every 2 days, with the negative control group receiving physiological saline alone. The positive control group was administered with C-176 (15 mg/kg) alone by intraperitoneal injection every 2 days, and the combination group was given licorice extracts by gavage (500 mg/kg) combined with C-176 (15 mg/kg) by intraperitoneal injection for 6 weeks (n = 8 per group). Following anesthesia, the mice were euthanized, liver tissues were collected for mRNA analysis, and serum was separated for ALT and AST detection. Various histologic staining techniques were used to determine the collagen deposition and histopathology in mice liver tissues, including hematoxylin-eosin (HE), Masson, Sirius Red staining, and immumohistochemical staining.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111149/
化学性质
| 分子量 | 358.09 |
| 分子式 | C11H7IN2O4 |
| CAS号 | 314054-00-7 |
| 溶解性（25°C） | DMSO 60 mg/mL |
| 储存条件 | 粉末型式 -20°C 3年；4°C 2年 溶于溶剂 -80°C 6个月；-20°C 1个月 |
| 运输方式 | 冰袋运输，根据产品的不同，可能会有相应调整。 |
储备液配制
*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 2.7926 mL | 13.963 mL | 27.9259 mL |
| 5 mM | 0.5585 mL | 2.7926 mL | 5.5852 mL |
| 10 mM | 0.2793 mL | 1.3963 mL | 2.7926 mL |
参考文献
[1] Simone M Haag, et al. Nature. Targeting STING with covalent small-molecule inhibitors.
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