STING agonist-4

STING agonist-4 is an agonist of stimulator of Interferon Genes (STING) receptor(IC50 of 20 nM).

STINGagonist-44 (Compound 4) is a potent and selective STING agonist with an EC50 value of 5.68 μM in THP1 cells and 2.212 μM in RAW cells for inducing IRF. It activates the STING pathway, leading to the production of type I interferons and pro-inflammatory cytokines (e.g., CXCL10, TNFα). STINGagonist-44 holds promise for cancer research.

STINGagonist-42 (compound 8a) is a potent STING agonist. It activates STING in THP1 and RAW 264.7 cells, with EC50 values of 0.06 μM and 14.15 μM, respectively.

STINGagonist-43 (Compound 67) is a selective STING agonist with an EC50 of 20.53 μM. It selectively enhances the cGAMP-dependent STING pathway activation by modulating STING oligomerization. STINGagonist-43 demonstrates antitumor activity in a B16.F10 mouse melanoma model and can be utilized in cancer immunotherapy research.

DiABZI-4 is an orally active STING agonist that exhibits broad-spectrum antiviral activity. It functions by activating STING to induce the production of pro-inflammatory cytokines and activation of lymphocytes. This action inhibits the replication of Influenza A virus (IAV), SARS-CoV-2, and Human Rhinovirus (HRV), with an EC50 range of 11.8-199 nM.

(S)-2-(1-Ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1-(2-hydroxy-2-phenylethyl)-1H-benzo[d]imidazole-5-carboxamide (compound 4) is a STING agonist containing the crucial amide benzimidazole (ABZI) component. It consistently inhibits the binding of 3 H-cGAMP to STING, with an apparent inhibition constant (IC50) of 14 μM. This compound is applicable in tumor research.

Ulevostinag isomer 4 (MK-1454 isomer 4) is an isomer of Ulevostinag, which functions as a STING agonist.

MSA-2 dimer, a selective and orally active non-nucleotide STING agonist with a dissociation constant (Kd) of 145 μM, demonstrates prolonged antitumor and immunogenic activity. It non-covalently binds to STING as a dimer, showing greater permeability compared to cyclic dinucleotide[1].

Cyclic diadenylate (c-di-AMP) sodium functions as a STING agonist by binding to the STING transmembrane protein, thus activating the TBK3-IRF3 signaling pathway. This activation prompts the production of type I IFN and TNF. Additionally, c-di-AMP sodium serves as a bacterial second messenger in Gram-positive bacteria, where it plays crucial roles in regulating cell growth, survival, and virulence, as well as the host immune response. It also acts as a potent mucosal adjuvant by stimulating both humoral and cellular responses [1] [2] [3] [4].

STING agonist D61 is a compound that activates the stimulator of interferon genes (STING), leading to the induction of IFN3-inducible secreted alkaline phosphatase (SEAP) and IFN-β-inducible reporter genes in cellular assays, with half-maximal effective concentrations (EC50s) of 52.9 and 116 nM, respectively. At concentrations of 4, 6, and 8 µM, D61 enhances the production of IFN-β and chemokine (C-X-C motif) ligand 10 (CXCL10) mRNA, as well as the phosphorylation of TANK-binding kinase 1 (TBK1), IRF3, and STING in THP-1 monocytes. Additionally, when administered at a dose of 0.25 mg/kg every other day, D61 effectively reduces tumor volume in a CT26 murine colon cancer model without impacting the body weight of the subjects.

STING agonist-33 (example 1), an agonist of STING (stimulator of interferon genes), is based on 4-ethyl-2-methylthiazole-5-carboxylic acid [1].