MSA-2
(Synonyms: 5,6-dimethoxy-γ-oxo-benzobthiophene-2-Butanoic Acid) 目录号 : GC61092
MSA-2是一种口服非核苷酸干扰素基因刺激因子（STING）激动剂，对人的STING亚型WT和HAQ的EC50分别为8.3和24μM。
Cas No.:129425-81-6
Sample solution is provided at 25 µL, 10mM.
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MSA-2 is an orally available non-nucleotide interferon gene stimulator (STING) agonist, with EC50 values of 8.3μM and 24μM for human STING subtypes WT and HAQ, respectively[1]. MSA-2 exhibits higher potency in the acidic tumor microenvironment, where the small molecule undergoes non-covalent dimerization to form a bioactive ligand[2]. MSA-2 in solution exists as monomers and noncovalent dimers in an equilibrium that holds a strong tendency towards the monomeric state[3].
In vitro, MSA-2 (20-50 μM) treatment of porcine PK-15 cells infected with Seneca Valley virus (SVV) for 24 hours dose-dependently inhibited SVV replication in the cells, activated the STING signaling pathway, and induced the expression of cytokines IFN-β, IL-6, and TNF-α[4]. MSA-2 (10, 50 μM) treatment of RAW264.7 cells for 24 hours increased intracellular IFN-β levels[5]. MSA-2 (25μM) treatment of human monocytes for 20 hours eliminated LPS-induced IL-10 and IL-19 production, while IL-1β and TNF-α were not inhibited[6].
In vivo, MSA-2 (p.o. 60 mg/kg or s.c. 50 mg/kg) treatment of mice with colon cancer models effectively inhibited tumor growth and increased levels of cytokines IFN-β, IL-6, and TNF-α in tumor cells[1]. MSA-2 (150 μg) administered intrathecally to mice with colon cancer and melanoma models significantly inhibited tumor growth, improved survival rates, enhanced the infiltration and activity of cytotoxic T cells in tumors, and contributed to tumor regression[5].
References:
[1] Pan B S, Perera S A, Piesvaux J A, et al. An orally available non-nucleotide STING agonist with antitumor activity[J]. Science, 2020, 369(6506): eaba6098.
[2] Liu J, Huang X, Ding J. Identification of MSA-2: An oral antitumor non-nucleotide STING agonist[J]. Signal Transduction and Targeted Therapy, 2021, 6(1): 18.
[3] Yang J, Luo Z, Ma J, et al. A next-generation STING agonist MSA-2: From mechanism to application[J]. Journal of Controlled Release, 2024, 371: 273-287.
[4] Lin H, Zhang R, Xiang H, et al. A Non-Nucleotide STING Agonist MSA-2 Synergized with Manganese in Enhancing STING Activation to Elicit Potent Anti-RNA Virus Activity in the Cells[J]. Viruses, 2023, 15(11): 2138.
[5] Wang M, Cai Y, He T, et al. Antitumor Effect of Platinum-Modified STING Agonist MSA-2[J]. ACS omega, 2024, 9(2): 2650-2656.
Kabelitz D, Zarobkiewicz M, Heib M, et al. Signal strength of STING activation determines cytokine plasticity and cell death in human monocytes[J]. Scientific Reports, 2022, 12(1): 17827.
MSA-2是一种口服非核苷酸干扰素基因刺激因子（STING）激动剂，对人的STING亚型WT和HAQ的EC50分别为8.3和24μM[1]。MSA-2在酸性肿瘤微环境中表现出更高的效力，其中小分子发生非共价二聚化形成生物活性配体[2]。MSA-2在溶液中以单体和非共价二聚体的形式存在，且该平衡强烈偏向于单体状态[3]。
在体外，MSA-2（20-50μM）处理塞内卡谷病毒（SVV）感染后的猪PK-15细胞24 h，剂量依赖性地抑制了细胞中SVV的复制，激活了STING信号通路，诱导了IFN-β、IL-6和TNF-α细胞因子的表达[4]。MSA-2（10、50μM）处理RAW264. 7细胞24h，均升高了胞内IFN-β的水平[5]。MSA-2（25μM）处理人单核细胞20h，发现脂多糖（LPS）诱导的IL-10和IL-19的产生被消除，而IL-1β和TNF-α不受抑制[6]。
在体内，MSA-2（p.o. 60 mg/kg or s.c. 50 mg/kg）治疗结肠癌模型小鼠，有效抑制了肿瘤生长，升高了肿瘤细胞中IFN-β、IL-6和TNF-α细胞因子的水平[1]。MSA-2（150μg）通过鞘内注射治疗结肠癌模型和黑色素瘤模型小鼠，均显著抑制了肿瘤生长并提高了生存率，增强了肿瘤中细胞毒性T细胞的浸润和活性，有助于诱导肿瘤消退[5]。
Cell experiment [1]: | |
Cell lines | PK-15 cells |
Preparation method | PK-15 cells were infected with SVV at a multiplicity of infection (MOI) of 10, incubated for 1 h to wash away unbound virus, and then treated with MSA-2 at concentrations of 20, 30, 40, and 50 μM for 24 h. |
Reaction Conditions | 20-50μM; 24 h |
Applications | The level of viral RNA was significantly decreased in MSA-2-treated cells in a dose-dependent manner. |
Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation method | MC38 cells were injected subcutaneously into 6-week old female C57BL/6 mice to establish tumor models. When the tumor volumes reached about 100mm3, the mice were randomly divided into 3 groups: control, MSA-2, and MSA-2-Pt. The mice were intratumor (i.t.) injected with control, 150μg of MSA-2, and 150μg of MSA-2-Pt for three doses |
Dosage form | 150μg; i.t. |
Applications | Treatment with MSA-2-Pt and MSA-2 significantly reduced tumor growth and increased survival when compared to the control group. |
References: [1] Lin H, Zhang R, Xiang H, et al. A Non-Nucleotide STING Agonist MSA-2 Synergized with Manganese in Enhancing STING Activation to Elicit Potent Anti-RNA Virus Activity in the Cells[J]. Viruses, 2023, 15(11): 2138. [2] Wang M, Cai Y, He T, et al. Antitumor Effect of Platinum-Modified STING Agonist MSA-2[J]. ACS omega, 2024, 9(2): 2650-2656. | |
| Cas No. | 129425-81-6 | SDF | |
| 别名 | 5,6-dimethoxy-γ-oxo-benzobthiophene-2-Butanoic Acid | ||
| Canonical SMILES | O=C(C1=CC(C(S1)=C2)=CC(OC)=C2OC)CCC(O)=O | ||
| 分子式 | C14H14O5S | 分子量 | 294.32 |
| 溶解度 | DMSO: 125 mg/mL (424.71 mM) | 储存条件 | 4°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 | 3.3977 mL | 16.9883 mL | 33.9766 mL |
| 5 mM | 0.6795 mL | 3.3977 mL | 6.7953 mL |
| 10 mM | 0.3398 mL | 1.6988 mL | 3.3977 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。
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Quality Control & SDS
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- Purity: >98.50%
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