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。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。
分子量 | 358.09 |
分子式 | C11H7IN2O4 |
CAS号 | 314054-00-7 |
溶解性 | 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。 |
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。
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/
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。
浓度/溶剂体积/质量 | 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 |
*吸湿的DMSO对产品的溶解度有显著影响,请使用新开封的DMSO;
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。
建议您制定动物给药及实验方案时,尽量参考已发表的相关实验文献(溶剂种类及配比众多,简单地溶解目的化合物,并不能解决动物给药依从性、体内生物利用度、组织分布等相关问题,未必能保证目的化合物在动物体内充分发挥生物学效用)。
体内实验的工作液,建议您现用现配,当天使用;如在配制过程中出现沉淀、析出现象,可以通过超声和(或)加热的方式助溶。
切勿一次性将产品全部溶解。
请在下面的计算器中,输入您的动物实验相关数据并点击计算,即可得到该实验的总需药量和工作液终浓度。
例如您给药剂量是10 mg/kg,平均每只动物的体重为20 g,每只动物的给药体积是100 μL,动物数量为20只,则该动物实验的总需药量为4 mg,工作液终浓度为2 mg/mL。
1:鉴于实验过程的损耗,建议您至少多配1-2只动物的量;
2:为该产品最终给药时的浓度。