PCC0208018 is a novel activator of effector T cells, enhancing T cell proliferation and activation to release interferon gamma (IFN-γ) and interleukin-2 (IL-2) without blocking the programmed cell death 1 (PD-1) programmed cell death-ligand 1 (PD-L1) binding and not directly affecting tumor cell viability in vitro.
M04 acts as a stimulator of interferon genes (STING) agonist, effectively inducing IFN reporter gene expression in HEK293T cells equipped with wild-type human STING. Its activity is specific, not affecting HEK293T cells with the R71H-G230A-R293Q (HAQ) human STING variant or mouse RAW 264.7 cells, showcasing allelic- and species-dependent effects at a concentration of 75 µM. This compound also stimulates the production of TNF-α, IL-10, IL-1β, and IL-12p70 in human peripheral blood mononuclear cells (PBMCs). At 50 µM, M04 enhances human monocyte-derived dendritic cells' expression of HLA-DR (MHC class II receptor) and co-stimulatory molecules CD40, CD80, and CD86, improving T cell cross-priming in an ex vivo assay.
DMI-9523 is nuclear factor NF-κB activation inhibitor. Antigen-stimulated human T lymphocytes produce significantly lower quantities of interferon-gamma and tumor necrosis factor-alpha after stimulation in vitro in the presence of DA-DKP. DA-DKP can modul
STING18 is a competitive ligand of stimulator of interferon genes (STING; IC50 = 0.068 μM in a radioligand binding assay).1 It inhibits cGAMP-induced IFN-β production (IC50 = 11 μM) but does not stimulate IFN-β production (EC50 = >30 μM) in THP-1 cells. |1. Siu, T., Altman, M.D., Baltus, G.A., et al. Discovery of a novel cGAMP competitive ligand of the inactive form of STING. Med. Chem. Lett. 10(1), 92-97 (2019).
5'-pApA is a linearized form of cyclic di-AMP, a bacterial second messenger that activates the host innate immune system through stimulator of interferon genes (STING).1,2,3,4It is a metabolite of cyclic di-AMP formedviahydrolysis by various phosphodiesterases (PDEs).55'-pApA is intended for use as a negative control for cyclic di-AMP signaling. 1.Burdette, D.L., Monroe, K.M., Sotelo-Troha, K., et al.STING is a direct innate immune sensor of cyclic-di-GMPNature478(7370)515-518(2011) 2.Parvatiyar, K., Zhang, Z., Teles, R.M., et al.DDX41 recognizes bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune responseNat. Immunol.13(12)1155-1161(2012) 3.Woodward, J.J., Iavarone, A.T., and Portnoy, D.A.c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon responseScience328(5986)1703-1705(2010) 4.Witte, C.E., Whiteley, A.T., Burke, T.P., et al.Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infectionmBio4(3)e00282-00213(2013) 5.Fahmi, T., Port, G.C., and Cho, K.H.c-di-AMP: An essential molecule in the signaling pathways that regulate the viability and virulence of gram-positive bacteriaGenes (Basel)8(8)197(2017)
CB-1158-analog, also known as Numidargistat-analog and INCB01158-analog, is a potent and orally active arginase inhibitor with IC50=89 nM) . CB-1158 blocked myeloid cell-mediated suppression of T cell proliferation in vitro and reduced tumor growth in multiple mouse models of cancer, as a single agent and in combination with checkpoint blockade, adoptive T cell therapy, adoptive NK cell therapy, and the chemotherapy agent gemcitabine. CB-1158 increased tumor-infiltrating CD8+ T cells and NK cells, inflammatory cytokines, and expression of interferon-inducible genes. CB-1158 may be potentially useful in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role. (see ADDITIONAL INFORMATION in this web page for CB-1158 structure confusion).
93-O17S is a chalcogen-containing cationic lipidoid.1It has been used in the synthesis of lipid nanoparticles (LPNs) for the delivery of Cre recombinase and ribonucleoproteins for genome editing in mice. LPNs containing 93-O17S have been used for the intratumoral delivery of cGAMP to enhance cross-presentation of tumor antigens and stimulation of interferon genes (STING) activation in a B16 F10 murine melanoma model.2 1.Li, Y., Yang, T., Yu, Y., et al.Combinatorial library of chalcogen-containing lipidoids for intracellular delivery of genome-editing proteinsBiomaterials178652-662(2018) 2.Chen, J., Qiu, M., Ye, Z., et al.In situ cancer vaccination using lipidoid nanoparticlesSci. Adv.7(19)eabf1244(2021)