diABZI STING agonist-1
目录号 : GC35853
diABZI STING agonist-1是干扰素基因刺激物（STING）途径的激动剂，其在人和小鼠中的EC50值分别为130nM 和186nM。
Cas No.:2138299-33-7
Sample solution is provided at 25 µL, 10mM.
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diABZI STING agonist-1 is an agonist of the stimulator of interferon genes (STING) pathway with EC50 values of 130nM in humans and 186nM in mice, respectively [1]. STING plays an important role in regulating the transcription of a large number of host defense genes (including type I IFN) and protecting cells from cancer development. diABZI STING agonist-1 demonstrated anti-tumor activity in mice with colon tumors [2].
In vitro, treatment of human NSCLC cell lines (H460 and A549) with diABZI STING agonist-1 (20nM) for 24, 48, and 72 hours significantly inhibited the proliferation of both cells. The inhibitory effect of diABZI STING agonist-1 combined with low-dose IR (2 Gy) on the proliferation of non-small cell lung cancer cells was closer to that of high-dose IR [2]. Treating melanoma cells with diABZI STING agonist-1 (21nM) in the culture medium for 24 hours will increase the phosphorylation levels of TBK1 and STING, and the phosphorylated STING will be located in the area near the nucleus. In addition, IRF3 was phosphorylated, indicating that the STING pathway was activated [3].
In vivo, a single subcutaneous injection of diABZI STING agonist-1 (2.5mg/kg/d) in mice caused a strong local inflammatory response and skin lesions, with elevated serum IL-10 levels. Systemic pretreatment with poly(I:C) in mice led to an exacerbated response to diABZI STING agonist-1, higher levels of systemic cytokines, more severe skin lesions, and delayed resolution of skin inflammation [4]. By treating OVX-induced osteoporosis mice with diABZI STING agonist-1 (0.5mg/kg; i.p.) for 3 times a week for 2 weeks, the concentrations of RANKL and CTX-I in serum and the RANKL/OPG ratio were significantly reduced. diABZI STING agonist-1 alleviates bone resorption induced by Ti particles and osteoporosis induced by ovarian ablation in vivo by inhibiting OC differentiation and function [5].
References:
[1] Ramanjulu J M, Pesiridis G S, Yang J, et al. Design of amidobenzimidazole STING receptor agonists with systemic activity[J]. Nature, 2018, 564(7736): 439-443.
[2] Xue A, Shang Y, Jiao P, et al. Increased activation of cGAS‐STING pathway enhances radiosensitivity of non‐small cell lung cancer cells[J]. Thoracic cancer, 2022, 13(9): 1361-1368.
[3] Chipurupalli S, Ganesan R, Dhanabal S P, et al. Pharmacological STING activation is a potential alternative to overcome drug-resistance in melanoma[J]. Frontiers in oncology, 2020, 10: 758.
[4] Pyclik M, Durslewicz J, Papinska J A, et al. STING agonist-induced skin inflammation is exacerbated with prior systemic innate immune activation[J]. International Journal of Molecular Sciences, 2023, 24(4): 4128.
[5] Huang Y, Zhang M, Zhang J, et al. diABZI and poly (I: C) inhibit osteoclastic bone resorption by inducing IRF7 and IFIT3[J]. Journal of Bone and Mineral Research, 2024, 39(8): 1132-1146.
diABZI STING agonist-1是干扰素基因刺激物（STING）途径的激动剂，其在人和小鼠中的EC50值分别为130nM 和186nM [1]。STING在调节大量宿主防御基因（包括I型IFN）的转录和保护细胞免受癌症发展中起重要作用。diABZI STING agonist-1在结肠肿瘤小鼠中显示出抗肿瘤活性[2]。
在体外，diABZI STING agonist-1（20nM）处理人NSCLC细胞系（H460和A549）24、48和72小时，两种细胞的增殖均受到明显抑制。diABZI STING agonist-1与低剂量的 IR（2Gy）联合使用对非小细胞肺癌细胞增殖的抑制效果更接近于高剂量IR的效果 [2]。将黑色素瘤细胞置于含有diABZI STING agonist-1（21nM）的培养基处理24小时，会促使TBK1和STING的磷酸化程度增加，并且磷酸化后的STING的定位会出现在细胞核附近区域。此外，IRF3发生磷酸化，这表明STING通路已被激活 [3] 。
在体内，diABZI STING agonist-1（2.5mg/kg/d）单次皮下注射小鼠，引起了强烈的局部炎症反应和皮肤病变，血清IL-10水平升高。用poly（I：C）全身预处理小鼠导致对diABZI STING agonist-1的反应加剧，全身细胞因子水平更高，皮肤病变更严重，皮肤炎症消退延迟 [4]。通过每周3次持续2周diABZI STING agonist-1（0.5mg/kg；i.p.）治疗OVX诱导的骨质疏松小鼠，显著降低了血清中RANKL、CTX-I的浓度和RANKL/OPG比值。diABZI STING agonist-1通过抑制OC分化和功能 ，在体内减轻Ti颗粒诱导的骨质溶解和卵巢切除诱导的骨质疏松症中的骨丢失 [5]。
| Cell experiment [1]: | |
Cell lines | Human NSCLC cell lines (H460 and A549) |
Preparation Method | Human NSCLC cell lines (H460 and A549) were cultured in RPMI 1640 (Gibco) and Ham's F-12 K (Procell), respectively. Irradiation (IR) was carried out with a 137Cs-irradiator (Gammacell-40, Atomic Energy of Canadian Inc.) at a dose rate of 0.9Gy/min. Cells were irradiated with 0, 2 and 4Gy γ-ray after pretreatment with diABZI STING agonist-1 trihydrochloride or DMSO for 2h. In this study, diABZI STING agonist-1 was used at a 20nM concentration according to previous studies. Briefly, cells (3 × 103 cells/well) were plated in 96-well plates and when they had grown to 70%–80% confluence, were treated with 20nM diABZI STING agonist-1 or DMSO. After 24, 48 and 72h treatment, respectively, cell counting kit-8 (CCK-8) (Biosharp) was added to each well. After incubation for 3h, absorbance at 450nm for each well was measured using a microplate reader (Infinite M200). |
Reaction Conditions | 20nM; 24、48 and 72h |
Applications | Compared to the control cells, the proliferation of both H460 and A549 cells was obviously inhibited by diABZI STING agonist-1. The inhibitory effect of diABZI STING agonist-1 combined with a low dose of IR (2Gy) on the proliferation of NSCLC cells was closer to that of a higher dose of IR. |
| Animal experiment [2]: | |
Animal models | BALB/cJ mice |
Preparation Method | Mice were injected on day 1 with a diABZI STING agonist-1 trihydrochloride (GLPBIO, Montclair, CA, USA) in 40% PEG300 (MilliporeSigma, St. Louis, MO, USA) (2.5mg/kg, 0.05mL/mouse, subcutaneous (sc) route) on a shaved back. One day before the diABZI STING agonist-1 injection, on day 0, some mice were pre-treated with poly (I:C) (HMW, InvivoGen Corp, San Diego, CA, USA) in saline (2mg/kg body weight, 0.2ml/mouse, intraperitoneal (ip) route). Mice injected with saline (ip) followed by 40% PEG300 (sc) or poly (I:C) (ip) followed by 40% PEG300 (sc) served as control groups. Tail bleeds were collected from all mice four hours after each injection on days 0 and 1. Sera were stored at -80 °C for cytokine analysis. The skin on the back of the mice was monitored daily for inflammatory changes. |
Dosage form | 2.5mg/kg/d; subcutaneous injection |
Applications | The diABZI STING agonist-1 caused a strong local inflammatory response and skin lesions in mice, with an increase in serum IL-10 levels. Systemic pretreatment with poly(I:C) in mice led to an intensified response to diABZI STING agonist-1, higher levels of systemic cytokines, more severe skin lesions, and delayed resolution of skin inflammation. |
References: | |
| Cas No. | 2138299-33-7 | SDF | |
| 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 | ||
| 分子式 | C42H51N13O7 | 分子量 | 849.94 |
| 溶解度 | DMSO : 100 mg/mL (117.66 mM; Need ultrasonic) | 储存条件 | Store at -20°C,protect from light |
| 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.1766 mL | 5.8828 mL | 11.7655 mL |
| 5 mM | 0.2353 mL | 1.1766 mL | 2.3531 mL |
| 10 mM | 0.1177 mL | 0.5883 mL | 1.1766 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。
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- Purity: >98.00%
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