PDIC-NS is an activator of stimulator of interferon genes (STING).[1] It increases the levels of reactive oxygen species (ROS) and induces apoptosis in LL/2 lung carcinoma cells when used at a concentration of 2.5 µM. PDIC-NS (2.5 µM) induces cell cycle arrest at the S phase, increases cytosolic levels of mitochondrial DNA (mtDNA), and increases levels of phosphorylated TANK-binding kinase 1 (Tbk1), interferon regulating factor 3 (Irf3), and STING in, as well as increases secretion of 2',3'-cGAMP and ATP from, LL/2 cells. It decreases tumor volume and weight and increases the percentage of intratumoral M1 macrophages and mature dendritic cells in an LL/2 mouse xenograft model when administered at a dose of 2 mg/kg twice per day. PDIC-NS (2.5 mg/kg twice per day) reduces lung weight and the number of lung metastases in wild-type and Sting1-/- mice in an LL/2 model of lung metastasis. It also increases serum levels of Ifn-β, Ifn-γ, Tnf-α, and chemokine (C-X-C motif) ligand 10 (Cxcl10), as well as increases the percentage of intratumoral CD4+, CD8+, and CD38+ T cells, in wild-type mice, and, to a lesser extent, in Sting1-/- mice, in the same model.
References:
[1].Zhao, X., Zheng, R., Zhang, B., et al.Sulfonated perylene as three-in-one STING agonist for cancer chemo-immunotherapyAngew. Chem. Int. Ed. Engl.63(11)e202318799(2024).