ML RR-S2 CDA (ammonium salt)

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).¹ 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; Item No. 17753), 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.

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1. Corrales, L., Glickman, L.H., McWhirter, S.M., et al. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 11(7), 1018-1030 (2015).