ADU-S100 disodium salt

Alias: ML RR-S2 CDA disodium salt ADU-S100 MIW815 disodium saltADU S100 MIW 815 disodium saltADUS100MIW-815 disodium salt2’3’-c-di-AM(PS)2(Rp,Rp)Bisphosphorothioate analog of c-di-AMP, Rp isomers
Cat No.:V32421 Purity: ≥98%
ADU-S100 disodium salt (MIW815; MIW-815; ML RR-S2-CDA)is the first agonist of stimulator of interferon genes (STING), with immunomodulatory and antitumor activities.
ADU-S100 disodium salt Chemical Structure CAS No.: 1638750-95-4
Product category: STING
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
Other Sizes

Other Forms of ADU-S100 disodium salt:

  • ADU-S100 ammonium salt
  • ADU-S100
Official Supplier of:
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Product Description

ADU-S100 disodium salt (MIW815; MIW-815; ML RR-S2-CDA) is the first agonist of stimulator of interferon genes (STING), with immunomodulatory and antitumor activities. ADU-S100 has high translational potential as a therapeutic intervention strategy to induce activation of the tumor microenvironment in multiple tumor types. ADU-S100 is the first STING pathway activator developed by Aduro in collaboration with Novartis. It is being evaluated clinical trials for the treatment of various cancers, as a single agent or in combination withother drugs such as ipilimumab and spartalizumab (PDR001), which are anti-PD-1 monoclonal antibody. ADU-S100 exhibits a higher affinity for binding to STING than c-di-AMP due to the presence of a 2’-5’, 3’-5’ mixed linkage, as found in endogenous human CDNs produced by cGAS (cyclic GMP-AMP (cGAMP) synthase). In addition, ADU-S100 can activate both human STING and murine STING. Furthermore, it contains two phosphorothioate diester linkages to protect against degradation by phosphodiesterases that are present in host cells or in the blood/systemic circulation. The Rp, Rp dithio diastereoisomer has been found to induce higher type I IFN production compared to the Rp/Sp dithio diastereoisomers or c-di-AMP. In vivo studies have demonstrated that 2’3’-c-di-AM(PS)2 (Rp,Rp) may potently prime tumor antigen-specific CD8+ T-cell responses and overcome antigen-enforced immune tolerance in combination with PD-L1 blockade.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
In THP-1 human monocytes, ADU-S100 produced more type I IFN than CDA. Disulfide mixed-linked cyclic dinucleotide (CDN) derivatives, on the other hand, effectively activated all five hSTING alleles, including the refractory hSTINGREF and hSTINGQ alleles (ML RR-CDA, ML RR-S2 CDG, and ML RR-S2 cGAMP). In comparison to endogenous ML cGAMP and the TLR3 agonist Poly I:C, ADU-S100 induced the highest expression of IFN-β and the proinflammatory cytokines TNF-α, IL-6, and MCP-1 on a molar equivalent basis. In mouse bone marrow macrophages (BMM), ADU-S100 was also found to induce STING aggregation and induce TBK1 and IRF3 phosphorylation. When compared to ML cGAMP, ADU-S100 induces noticeably higher levels of IFN-α [1].
ln Vivo
ADU-S100 outperformed endogenous ML cGAMP in its anti-tumor control capacity. In B16 tumor-bearing mice, a dose response study of ADU-S100 compounds was carried out to ascertain the best anti-tumor dose level that would maximize tumor antigen-specific CD8+ T cell responses and increase long-term survival to 50%[1].
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
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C₂₀H₂₂N₁₀NA₂O₁₀P₂S₂
Molecular Weight
734.51
CAS #
1638750-95-4
Related CAS #
ADU-S100 ammonium salt;1638750-96-5;ADU-S100 enantiomer ammonium salt;ADU-S100;1638241-89-0
SMILES
O[C@@H]1[C@@H](CO[P@@]([S-])(O[C@H]2[C@@H](O)[C@H](N3C4=C(C(N)=NC=N4)N=C3)O[C@@H]2CO5)=O)O[C@@H](N6C7=C(C(N)=NC=N7)N=C6)[C@@H]1O[P@@]5([S-])=O.[Na+].[Na+]
InChi Key
GDWOOOCBNOMMTL-ITQXCAEYSA-L
InChi Code
InChI=1S/C20H24N10O10P2S2.2Na/c21-15-9-17(25-3-23-15)29(5-27-9)19-12(32)13-8(38-19)2-36-42(34,44)40-14-11(31)7(1-35-41(33,43)39-13)37-20(14)30-6-28-10-16(22)24-4-26-18(10)30/h3-8,11-14,19-20,31-32H,1-2H2,(H,33,43)(H,34,44)(H2,21,23,25)(H2,22,24,26)/q2*+1/p-2/t7-,8-,11-,12-,13-,14-,19-,20-,41-,42-/m1../s1
Chemical Name
(2',3')-Rp,Rpc-diAMPS disodium
Synonyms
ML RR-S2 CDA disodium salt ADU-S100 MIW815 disodium saltADU S100 MIW 815 disodium saltADUS100MIW-815 disodium salt2’3’-c-di-AM(PS)2(Rp,Rp)Bisphosphorothioate analog of c-di-AMP, Rp isomers
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
H2O : ~100 mg/mL (~136.15 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 25 mg/mL (34.04 mM) (saturation unknown) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.3615 mL 6.8073 mL 13.6145 mL
5 mM 0.2723 mL 1.3615 mL 2.7229 mL
10 mM 0.1361 mL 0.6807 mL 1.3615 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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