M04

M04 is an agonist of stimulator of interferon genes (STING).¹ It induces IFN reporter gene expression in HEK293T cells expressing wild-type human STING but not in HEK293T cells expressing the R71H-G230A-R293Q (HAQ) human STING variant nor in mouse RAW 264.7 cells, indicating allelic- and species-dependent activities, at 75 µM. M04 induces the production of TNF-α, IL-10, IL-1β, and IL-12p70 in human peripheral blood mononuclear cells (PBMCs). It increases the percentage of isolated human monocyte-derived dendritic cells expressing the MHC class II cell surface receptor HLA-DR and the co-stimulatory molecules CD40, CD80, and CD86, as well as increases T cell cross-priming of the same cells in an ex vivo assay, when used at a concentration of 50 µM.

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1. Abraham, J., Botto, S., Mizuno, N., et al. Characterization of a novel compound that stimulates STING-mediated innate immune activity in an allele-specific manner. Front. Immunol. 11, 1430 (2020).