ADU-S100 disodium salt
(Synonyms: MIW815 disodium salt; ML RR-S2 CDA disodium salt) 目录号 : GC39161
ADU-S100 disodium salt（MIW815 disodium salt）是干扰素基因刺激蛋白（STING）的激活剂，Kd为4.61±0.42μM。
Cas No.:1638750-95-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment [1]: |
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Cell lines |
GBM cells |
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Preparation method |
A single-cell suspension of GBM cells was seeded at 2,000 cells/well in ultra-low-attachment 96-well plates and incubated for 24h to allow sphere formation. PBMCs were then added with the different ADU-S100 disodium salt concentrations(0, 6, 12.5, 25, 50, 100μM) and treatment was repeated 3d later. Cells were then incubated for another 3d(total = 6d of coculture). |
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Reaction Conditions |
0, 6, 12.5, 25, 50, 100μM; 6d |
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Applications |
This showed that ADU-S100 disodium salt is not toxic to GBM neurospheres. In contrast, in the presence of PBMCs we observed an ADU-S100 disodium salt concentration-dependent immune cell killing of the GBM neurospheres. |
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Animal experiment [2]: |
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Animal models |
BALB/c mice |
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Preparation method |
CT26 cells were injected SC into the right flank of the animals. Tumor-bearing mice were randomly assigned to five groups: (a) Control group received 20µl PBS; (b, c) tumor groups treated with ADU-S100 disodium salt at various dosages of 20 or 40µg; (d) tumor group treated with 40 µg of CpG ODN, and combination group (e) received 20 µg ADU-S100 and 20µg CpG ODN simultaneously. The agonists were injected intratumorally on the 10th and 16th days after tumor inoculation. |
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Dosage form |
20 or 40 µg; s.c. |
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Applications |
significant tumor regression was observed in all treatment groups compared to the control group. ADU-S100 disodium salt at 40 µg dose suppressed the CT-26 tumor growth more effectively than at 20 µg dosage. |
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References: [1] Berger G, Knelson E H, Jimenez-Macias J L, et al. STING activation promotes robust immune response and NK cell–mediated tumor regression in glioblastoma models[J]. Proceedings of the National Academy of Sciences, 2022, 119(28): e2111003119. [2]Hajiabadi S, Alidadi S, Ghahramani Senoo M M, et al. Therapeutic effects of ADU-S100 as STING agonist and CpG ODN1826 as TLR9 agonist in CT-26 model of colon carcinoma[J]. Iranian Journal of Veterinary Science and Technology, 2023, 15(2): 29-37. |
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ADU-S100 disodium salt (MIW815 disodium salt) is an activator of stimulatory interferon gene (STING) protein with a Kd of 4.61±0.42μM[1]. The mechanism of action of ADU-S100 disodium salt is to activate the STING pathway by simulating the effect of cyclic GMP-AMP (cGAMP), thereby inducing the production of inflammatory cytokines such as IFN-β[2]. ADU-S100 disodium salt shows higher anti-tumor ability than endogenous ML cGAMP [3].
In vitro, ADU-S100 disodium salt (0-100µM) treated glioblastoma (GBM) cells without toxicity, but in the presence of PBMC, ADU-S100 produced immune-mediated cytotoxicity against GBM cells at 12.5 and It is effective between 50µM and less effective at 100µM[4]. ADU-S100 disodium salt stimulated the THP-1 Dual cell line for 48 hours, and the EC50 values of activated cell IRF 3 and NF-κB pathways were 3.031 and 4.839µg/mL respectively [5].
In vivo, ADU-S100 disodium salt (50µg) was administered via intracranial injection to GL 261 and CT-2A tumor model mice 3 days after treatment, causing suppression of microglia and T cell populations, as well as NK and inflammatory responses. In the infiltration of immune cells, the proportion of T cells recovered 7 days after treatment and increased compared with the baseline level [4]. ADU-S100 disodium salt (20 or 40µg) was treated by subcutaneous injection in colon cancer model mice, which effectively inhibited the growth of CT-26 tumors, significantly increased the number of lymphocytes, and prevented tumor metastasis to liver and spleen tissues[6].
References:
[1]Jekle A, Thatikonda S, Stevens S, et al. Abstract 4520: Preclinical characterization of ALG-031048, a novel STING agonist with potent anti-tumor activity in mice[C]//Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24.
[2]Jneid B, Bochnakian A, Hoffmann C, et al. Selective STING stimulation in dendritic cells primes antitumor T cell responses[J]. Science Immunology, 2023, 8(79): eabn6612.
[3]Corrales L, et al. Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity[J]. Cell Rep. 2015 May 19;11(7):1018-30.
[4]Berger G, Knelson E H, Jimenez-Macias J L, et al. STING activation promotes robust immune response and NK cell–mediated tumor regression in glioblastoma models[J]. Proceedings of the National Academy of Sciences, 2022, 119(28): e2111003119.
[5]Ji N, Wang M, Tan C. Liposomal delivery of MIW815 (ADU-S100) for potentiated STING activation[J]. Pharmaceutics, 2023, 15(2): 638.
[6]Zaidi A H, Kelly R J, Gorbunova A, et al. Intratumoral immunotherapy with STING agonist, ADU-S100, induces CD8+ T-cell mediated anti-tumor immunity in an esophageal adenocarcinoma model[J]. Oncotarget, 2021, 12(4): 292.
ADU-S100 disodium salt（MIW815 disodium salt）是干扰素基因刺激蛋白（STING）的激活剂，Kd为4.61±0.42μM[1]。ADU-S100 disodium salt的作用机制是通过模拟环状GMP-AMP（cGAMP）的作用，激活STING途径，进而诱导IFN-β等炎症性细胞因子的产生[2]。ADU-S100 disodium salt比内源性ML cGAMP显示出更高的抗肿瘤能力[3]。
在体外，ADU-S100 disodium salt（0-100µM）处理胶质母细胞瘤（GBM）细胞没有毒性，但在PBMC存在下，ADU-S100对GBM细胞产生了免疫介导的细胞毒性，在12.5和50 µM之间有效，而在100µM时效果降低[4]。ADU-S100 disodium salt刺激THP-1 Dual细胞系48h，活化细胞IRF 3和NF-κ B途径的EC50值分别为3.031、4.839µg/mL[5]。
在体内，ADU-S100 disodium salt（50µg）通过颅内注射给予GL 261和CT-2A肿瘤模型小鼠，治疗后3d，引起了小胶质细胞和T细胞群体的抑制，以及NK和炎性免疫细胞的浸润，治疗后7d，T细胞比例恢复，与基线水平相比有所增加[4]。ADU-S100 disodium salt（20 or 40µg）通过皮下注射治疗结肠癌模型小鼠，有效地抑制了CT-26肿瘤生长，显著增加了淋巴细胞的数量，且阻止了肿瘤转移到肝、脾组织中[6]。
| Cas No. | 1638750-95-4 | SDF | |
| 别名 | MIW815 disodium salt; ML RR-S2 CDA disodium salt | ||
| Canonical SMILES | [O-]C([C@](CO[P@]1(S)=O)([H])O2)([H])[C@](O[P@](S)(OC[C@](O[C@@H](N3C4=NC=NC(N)=C4N=C3)[C@@H]5[O-])([H])[C@@]5([H])O1)=O)([H])[C@@H]2N6C7=NC=NC(N)=C7N=C6.[Na+].[Na+] | ||
| 分子式 | C20H22N10Na2O10P2S2 | 分子量 | 734.51 |
| 溶解度 | Water: 100 mg/mL (136.15 mM; ultrasonic and adjust pH to 7 with NaOH) | 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。 |
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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 | 1.3615 mL | 6.8073 mL | 13.6145 mL |
| 5 mM | 0.2723 mL | 1.3615 mL | 2.7229 mL |
| 10 mM | 0.1361 mL | 0.6807 mL | 1.3615 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 |
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| % 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，
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2.
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