ADU-S100 ammonium salt (MIW815 ammonium salt), an activator of stimulator of interferon genes ( STING ), leads to potent and systemic tumor regression and immunity
In Vitro
ADU-S100 ammonium salt has several features that improve both stability and lipophilicity, promoting significantly increased STING signaling as compared to endogenous and pathogen-derived cyclic dinucleotides (CDNs). 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 hSTING REF and hSTING Q 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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% . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
