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ML RR-S2 CDA is a synthetic cyclic dinucleotide (CDN) that contains non-canonical 2''5''-phosphodiester bonds and is an activator of stimulator of interferon genes (STING). It contains mixed linkages (ML) with both 2''5'' and 3''5'' linkages, which leads to increased thermal stability of human STING in a differential scanning fluorimetry (DSF) assay. ML RR-S2 CDA increases type I interferon production by THP-1 human monocytes relative to unmodified cyclic di-AMP (CDA; ), indicating the ML enhances its action at human STING. It induces expression of IFN-β and the pro-inflammatory cytokines TNF-α, IL-6, and Mcp-1 in murine bone marrow macrophages (BMM) isolated from wild-type, but not STING^-/-, mice. ML RR-S2 CDA also induces IFN-β expression in peripheral blood mononuclear cells (PBMCs) isolated from donors carrying STING^WT/WT, STING^WT/REF, and STING^WT/HAQ alleles. In vivo, ML RR-S2 CDA initiates tumor regression and prevents tumor growth upon tumor cell reimplantation in 4T1 murine mammary and CT26 murine colon cancer models.

2’3’-c-di-AM(PS)2 (Rp,Rp) ammonium salt (ADU-S100 ammonium salt), an activator of stimulator of interferon genes (STING), leads to potent and systemic tumor regression and immunity[1].

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[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. DOI:10.1016/j.celrep.2015.04.031