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ADU-S100

CAS No. : 1638241-89-0

產(chǎn)品活性：ADU-S100 (MIW815), an activator of stimulator of interferon genes (STING), leads to potent and systemic tumor regression and immunity.

研究領(lǐng)域：Immunology/Inflammation

作用靶點(diǎn)：STING

In Vitro: ADU-S100 is unstable in its free base form. ADU-S100 ammonium salt (HY-12885B) improves 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 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.

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%.

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