STING

STING is a transmembrane protein that is found in the endoplasmic reticulum. When cyclic dinucleotides are directly bound to it, the protein changes its conformation, which sets off a chain of events that includes the activation of TBK1, the phosphorylation of IRF-3, and the generation of IFN-β and other cytokines. One potential therapeutic approach to support wide tumor-initiated T cell priming toward tumor antigen repertoire is the direct activation of the STING pathway[1].

[1]. Corrales L, et al. Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity. Cell Rep. 2015 May 19;11(7):1018-30.

ADU-S100 (MIW815) is a synthetic cyclic dinucleotide (CDN) agonist (activator) that activates the interferon gene-stimulating factor (STING) receptor. The STING receptor is a key receptor for activating the innate (endogenous) immune system. ADU-S100 (MIW815) activates all known human and mouse STING receptors and effectively induces the expression of cytokines and chemokines, thereby generating a potent and durable antigen-specific T cell-mediated immune response against cancer cells. MIW815, a STING-activating cyclic dinucleotide agonist listed in the DrugBank database, is a synthetic cyclic dinucleotide (CDN) and an agonist of the interferon gene-stimulating factor protein (STING; transmembrane protein 173; TMEM173), possessing potential immunomodulatory and antitumor activity. After intratumoral injection, the STING agonist MIW815 binds to STING and activates the STING-mediated signaling pathway. This activates the immune response by activating certain immune cells, including dendritic cells (DCs), which in turn induces the expression of cytokines and chemokines, ultimately leading to an antigen-specific T cell-mediated immune response against cancer cells. STING is a transmembrane protein that can activate immune cells in the tumor microenvironment and plays a key role in the activation of the innate immune system.

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Tumor-initiated spontaneous T cell initiation depends on IFN-β produced by tumor-resident dendritic cells. Based on recent observations that IFN-β expression depends on the activation of the host STING pathway, we hypothesize that direct activation of the STING pathway by intratumoral (IT) injection of a specific agonist will produce an effective antitumor therapeutic effect. After a proof-of-concept study using the mouse STING agonist DMXAA showed significant therapeutic effects, we synthesized cyclic dinucleotide (CDN) derivatives that can activate all human STING alleles and mouse STING. Intrathecal injection of STING agonists significantly inhibited established tumors in mice and produced a strong systemic immune response that could clear distant metastases and provide durable immune memory. Synthetic CDN has great potential for translational application as a cancer therapeutic agent. [1]

C20H30N12O10P2S2

724.60

ADU-S100 disodium salt;1638750-95-4;ADU-S100 ammonium salt;1638750-96-5;ADU-S100;1638241-89-0

Typically exists as solid at room temperature

MIW815 enantiomer ammonium salt; ADU-S100 enantiomer ammonium salt;ML RR-S2 CDA enantiomer ammonium salt

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO :~50 mg/mL (~69.00 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (3.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (3.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)