1. Immunology/Inflammation
  2. STING
  3. ADU-S100 disodium salt

ADU-S100 disodium salt (Synonyms: ML RR-S2 CDA disodium salt; MIW815 disodium salt)

Cat. No.: HY-12885A
Handling Instructions

ADU-S100 disodium salt is an activator of stimulator of interferon genes (STING).

For research use only. We do not sell to patients.

ADU-S100 disodium salt Chemical Structure

ADU-S100 disodium salt Chemical Structure

CAS No. : 1638750-95-4

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Description

ADU-S100 disodium salt is an activator of stimulator of interferon genes (STING).

IC50 & Target

STING[1]

In Vitro

ADU-S100 shows enhanced type I IFN production over CDA in THP-1 human monocytes. In contrast, the dithio, mixed-linkage cyclic dinucleotide (CDN) derivatives (ML RR-CDA, ML RR-S2 CDG, and ML RR-S2 cGAMP) potently activate all five hSTING alleles, including the refractory hSTINGREF and hSTINGQ alleles. ADU-S100 induces the highest expression of IFN-β and the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1 on a molar equivalent basis, as compared to endogenous ML cGAMP and the TLR3 agonist poly I:C. ADU-S100 is also found to induce aggregation of STING and induce phosphorylation of TBK1 and IRF3 in mouse bone marrow macrophage (BMM). ADU-S100 induces significantly higher levels of IFN-α when compared to ML cGAMP[1].

In Vivo

ADU-S100 shows higher anti-tumor control than the endogenous ML cGAMP. A dose response of the ADU-S100 compound is performed in B16 tumor-bearing mice, which identifies an optimal antitumor dose level that also elicites maximum tumor antigen-specific CD8+ T cell responses, and improves long-term survival to 50%[1].

Molecular Weight

734.51

Formula

C₂₀H₂₂N₁₀Na₂O₁₀P₂S₂

CAS No.

1638750-95-4

SMILES

[O-]C([[email protected]](CO[[email protected]]1(S)=O)([H])O2)([H])[[email protected]](O[[email protected]](S)(OC[[email protected]](O[[email protected]@H](N3C4=NC=NC(N)=C4N=C3)[[email protected]@H]5[O-])([H])[[email protected]@]5([H])O1)=O)([H])[[email protected]@H]2N6C7=NC=NC(N)=C7N=C6.[Na+].[Na+]

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

References
Cell Assay
[1]

Cryopreserved hPBMCs are thawed and 1×106 cells per well are plated in a 96 well plate in RPMI media supplemented with 10% FBS, 1% non-essential amino acids, 1% penicillin/streptomycin, L-glutamine, 10 mM HEPES buffer, 1 mM Sodium Pyruvate, 0.055 mM β-ME at 37°C with 5% CO2. Cells are stimulated with 10 μM ADU-S100 or ML cGAMP for 6 hours and supernatants are harvested. Supernatants are diluted 1:2 and assayed for IFN-α protein using Cytometric Bead Array (CBA) Human Flex Set. Data is collected using a FACSVerse cytometer and analyzed by FCAP Array Software[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Mice[1]
WT C57BL/6 mice are inoculated with 5×104 B16.F10 cells in the left flank (n=8). When tumor volumes are 100 mm3 mice receive three IT doses of either ML RR-S2 CDG (25 μg), ADU-S100 (50 μg), or HBSS as control. WT C57BL/6 mice are inoculated with 5×104 B16.F10 cells in the left flank (n=5). When tumor volumes are 100 mm3 they received three IT doses of ADU-S100 at 5, 25, 50 or 100 μg or HBSS as control. WT C57BL/6 mice are inoculated with 5×104 B16.F10 cells in the left flank (n=8). When tumor volumes are 100 mm3 they receive three IT doses of 100 μg ADU-S100 or HBSS as control. Treatments are administered on days 13, 17 and 20 and tumor measurements are taken twice weekly. Results are shown as percent survival by Log-rank (Mantel-Cox) test (A and C)[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
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ADU-S100 disodium salt
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