EVALUATION OF BIOLOGICAL ACTIVITY OF SAD-2: A NEW AND ORIGINAL STING ACTIVATOR

BACKGROUND: Targeted STING activators have high potential in cancer immunotherapy. Immunoconjugates are one of the promising formats of targeted delivery. Known compounds such as MSA-2 do not have sufficient activity for their use in immunoconjugates, therefore, the development of new more active compounds is required. Therefore, it is necessary to develop new, more active compounds.

AIM: To study the biological activity of the new compound, SAD-2, and evaluate its potential for the development of a novel immunobiological treatment for malignant neoplasms.

METHODS: Modern methods of fine organic synthesis and analysis of the resulting compounds are used. Compound MSA-2 was prepared from veratrole using a multistep synthetic process. Compound SAD-2 was then synthesized from MSA-2 through esterification with isopropyl alcohol in the presence of thionyl chloride. Antiproliferative activity was assessed for both compounds using MTT assays on colorectal cancer cell lines and human peripheral blood mononuclear cells. Interferon beta gene expression was evaluated using real-time polymerase chain reaction (PCR) on the human monocyte cell line, THP-1.

RESULTS: A new compound, SAD-2, has been developed that is 200-500 times more effective than the known compound, MSA-2, in terms of its antiproliferative activity, as measured by the IC₅₀ value. Both MSA-2 and SAD-2 exhibit their activity only in the presence of immune cells. In terms of the relative induction of the IFNB1 gene, SAD-2 outperforms MSA-2 between 5 and 60 times, depending on the duration of incubation.

CONCLUSION: The new compound, SAD-2, is a promising candidate for the development of drugs that can activate the STING signaling pathway in tumor cells, in the form of an immunoconjugate.