2',3'-cGAMP 钠（2'-3'-环状 GMP-AMP 钠）是哺乳动物细胞中的内源性 cGAMP。
货号:ajcx16422
CAS:N/A
分子式:C20H22N10Na2O13P2
分子量：718.37
溶解度:H2O: 50 mg/mL (69.60 mM); DMSO: 12.5 mg/mL (17.40 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

2′3′-cGAMP sodium is a second messenger that binds and activates the adaptor protein stimulator of interferon (STING), which triggers the innate immune response^[1]. As a STING agonist, the small molecule 2′3′-cGAMP sodium plays pivotal roles in antiviral defense and has adjuvant applications, and anti-tumor effects. 2′3′-cGAMP sodium and its analogs are thus putative targets for immunotherapy and are currently being tested in clinical trials to treat solid tumors.

2′3′-cGAMP sodium is capable of enhancing the proinflammatory activation of cultured Wild-type (WT) macrophages. Unlike in macrophages (BMDM), 2′3′-cGAMP sodium treatment displayed anti-inflammatory effects in both WT primary mouse hepatocytes and differentiated 3T3-L1 adipocytes. Specifically, LPS-induced JNK p46 and NF-κB p65 phosphorylation states and IL-1β and TNFα mRNAs in 2′3′-cGAMP sodium -treated WT primary mouse hepatocytes were significantly lower than their respective levels in control-treated hepatocytes. In 3T3-L1 adipocytes, the anti-inflammatory effect of 2′3′-cGAMP sodium was even more pronounced. In particular, LPS-induced JNK p46 phosphorylation states in 2′3′-cGAMP sodium -treated adipocytes were markedly lower than in control-treated adipocytes, and were comparable with JNK p46 phosphorylation states in 2′3′-cGAMP sodium -treated adipocytes in the absence of LPS induction^[2].

2′3′-cGAMP sodium and CpG-C co-administration adjuvants had a synergistic effect to establish a shift towards the Th1(T helper type 1) immune response, and leading to reduced tumor growth. This vaccine formulation could be a promising therapeutic candidate vaccine for HPV 16 established infections and HPV-associated tumors^[3]. 2′3′-cGAMP sodium led to a marked CD8 T cell increase in tumors; combined treatment further increased the percentage of CD8 T cells^[4].

参考文献:
[1]. Su M, Zheng J, Gan L, Zhao Y, Fu Y, Chen Q. Second Messenger 2’3’-Cyclic GMP-AMP (2’3’-cGAMP):Synthesis, Transmission, and Degradation. Biochem Pharmacol (2022) 198:114934. doi: 10.1016/j.bcp.2022.114934
[2]. X. Guo, C. Shu, H. Li, et al. Cyclic GMP-AMP ameliorates diet-induced metabolic dysregulation and regulates proinflammatory responses distinctly from STING activation Sci Rep, 7 (2017), p. 6355
[3]. Dorostkar, F.; Arashkia, A.; Roohvand, F. et al. Co-administration of 2’3’-cGAMP STING activator and CpG-C adjuvants with a mutated form of HPV 16 E7 protein leads to tumor growth inhibition in the mouse model. Infect. Agents Cancer 2021, 16, 7.
[4]. Lai J, Fu Y, Tian S, et al. Zebularine elevates STING expression and enhances cGAMP cancer immunotherapy in mice. 2021. Mol Ther 29: 1758–1771.

Protocol:

Cell experiment [1]:
Cell lines	Bone marrow cells isolated from WT mice and STINGgtmice
Preparation Method	Bone marrow cells were isolated from WT mice and STINGgtmice and differentiated into macrophages (BMDM)，After differentiation, both WT BMDM and STINGgtBMDM were treated with or without 2’,3’-cGAMP sodium (20?μg/ml) for 24h in the presence or absence of lipopolysaccharide (LPS) (20 ng/ml) for the last 6 hr. In parallel, both WT BMDM and STINGgt BMDM were treated with commercial 2’,3’-cGAMP sodium
Reaction Conditions	Cells treated at a dose of 20?μg/ml for 0, 6, 24, and/or 48h or at a dose of 0, 5, 20 and/or 40?μg/ml for 24h.
Applications	WT BMDM treated with enzymatically synthesized 2’,3’-cGAMP sodium and observed significant increases in LPS-stimulated proinflammatory signaling through JNK p46 and NF-κB p65 and expression of IL-1β, IL-6, and TNFα.
Animal experiment [2]:
Animal models	Female nude Foxn1 mice 6-week-old
Preparation Method	B16F10 melanoma tumor cells were injected into the right shoulder of female mice to establish tumors. At 7 days after tumor cell inoculation, the mice were treated with zebularine alone, 2’,3’-cGAMP sodium alone, or the combination of both. A final concentration of 2.5 mg/mL zebularine was added to drinking water for 10 days until the mice were collected for conducting further experiments. A total of 100 μL of 10μg 2’,3’-cGAMP sodium in PBS at the indicated concentrations was injected into the site next to tumor. 2’,3’-cGAMP sodium treatment was repeated three times with 4-day intervals.
Dosage form	10μg, three times every the 4thday, injected into the site next to tumor
Applications	At this time point, we saw a similar effect from triple combination compared to the 2’,3’-cGAMP sodium +zebularine group. However, further statistics on the tumor growth and survival curve showed that triple combination led to more robust control of tumor growth and markedly extended survival in the B16F10 model.
参考文献: [1]. X. Guo, C. Shu, H. Li, et al. Cyclic GMP-AMP ameliorates diet-induced metabolic dysregulation and regulates proinflammatory responses distinctly from STING activation Sci Rep, 7 (2017), p. 6355 [2]. Lai J, Fu Y, Tian S, Huang S, Luo X, Lin L, Zhang X, Wang H, Lin Z, Zhao H et al (2021) Zebularine elevates STING expression and enhances cGAMP cancer immunotherapy in mice. Mol Ther 29: 1758–1771