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

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

Cat. No.: HY-12885 Purity: 99.23%
Handling Instructions

ADU-S100 (ML RR-S2 CDA; MIW815), an activator of stimulator of interferon genes (STING), leads to potent and systemic tumor regression and immunity.

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

ADU-S100 Chemical Structure

ADU-S100 Chemical Structure

CAS No. : 1638241-89-0

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Based on 1 publication(s) in Google Scholar

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Description

ADU-S100 (ML RR-S2 CDA; MIW815), an activator of stimulator of interferon genes (STING), leads to potent and systemic tumor regression and immunity[1].

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].

Clinical Trial
Molecular Weight

690.54

Formula

C₂₀H₂₄N₁₀O₁₀P₂S₂

CAS No.

1638241-89-0

SMILES

OC1([H])[[email protected]](O[[email protected]](S)(OC[[email protected]](O[[email protected]@H](N2C3=NC=NC(N)=C3N=C2)[[email protected]@H]4O)([H])[[email protected]@]4([H])O5)=O)([H])[[email protected]](N6C7=NC=NC(N)=C7N=C6)O[[email protected]]1([H])CO[[email protected]]5(S)=O

Shipping

Room temperature in continental US; may vary elsewhere

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 2 mg/mL (2.90 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.4481 mL 7.2407 mL 14.4814 mL
5 mM --- --- ---
10 mM --- --- ---
*Please refer to the solubility information to select the appropriate solvent.
References
Cell Assay
[1]

Cryopreserved hPBMCs are thawed and 1×106 cells per well are plated in a 96 well plate in RPMI media. 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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