ML RR-S2 CDA(ADU-S100)| CAS 1638750-96-5|DC Chemicals

Cas No.:	1638750-96-5
Chemical Name:	Adenosine, [P(R)]-5'-O-[(R)-hydroxymercaptophosphinyl]-P-thioadenylyl-(2'→5')-, cyclic nucleotide, ammonium salt (1:2)
Synonyms:	STING-Inducer-1 ammonium salt
SMILES:	OC1([H])[C@](O[P@](S)(OC[C@](O[C@@H](N2C3=NC=NC(N)=C3N=C2)[C@@H]4O)([H])[C@@]4([H])O5)=O)([H])[C@H](N6C7=NC=NC(N)=C7N=C6)O[C@]1([H])CO[P@]5(S)=O.N.N
Formula:	C₂₀H₃₀N₁₂O₁₀P₂S₂
M.Wt:	724.604124
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	ADU-S100 ammonium salt is an activator of stimulator of interferon genes (STING).
Target:	STING[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].
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].
Cell Assay:	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].
Animal Administration:	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).
References:	[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.

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Adenosine, [P(R)]-5'-O-[(R)-hydroxymercaptophosphinyl]-P-thioadenylyl-(2'→5')-, cyclic nucleotide, ammonium salt (1:2)