rig-1

RIG-1 modulator 1 is useful for the treatment of viral infections including influenza virus, HBV, HCV and HIV.

KIN1408 is an antiviral small molecule compound that is an agonist of the RIG-1-like receptor (RLR) pathway and is able to drive the activation of IRF3 (Interferon Regulatory Factor 3) to induce the expression of innate immunity genes (e.g., MDA5, RIG-1, Mx1, IRF7, and IFIT1), and to promote the nuclear translocation of IRF3 by targeting MAVS (Mitochondrial Antiviral Signaling Protein) or its upstream IRF3 nuclear translocation by targeting MAVS (mitochondrial antiviral signaling protein) or its upstream factors. KIN1400 is the parent, and KIN1409 is a derivative.

CU-32 is an inhibitor of cyclic GMP-AMP (cGAMP) synthase (cGAS; IC50= 0.45 μM).1It reduces DNA-, but not Sendai virus-, induced dimerization of IFN regulatory factor 3 in THP-1 cells, indicating selectivity for the cGAS DNA sensing pathway over the RIG-I-MAVS RNA sensing pathway. It is also selective for cGAS over toll-like receptors (TLRs) at 50 μM. CU-32 decreases IFN-stimulatory DNA-induced production of IFN-β in THP-1 cells when used at concentrations of 10, 30, and 100 μM. 1.Padilla-Salinas, R., Sun, L., Anderson, R., et al.Discovery of small-molecule cyclic GMP-AMP synthase inhibitorsJ. Org. Chem.85(3)1579-1600(2020)

CU-76 is an inhibitor of cyclic GMP-AMP synthase (cGAS; IC50= 0.24 μM).1It reduces DNA-, but not Sendai virus-, induced dimerization of IFN regulatory factor 3 in THP-1 cells, indicating selectivity for the cGAS DNA sensing pathway over the RIG-I-MAVS RNA sensing pathway. CU-76 decreases IFN-stimulatory DNA-induced production of IFN-β in THP-1 cells when used at concentrations of 10, 30, and 100 μM. 1.Padilla-Salinas, R., Sun, L., Anderson, R., et al.Discovery of small-molecule cyclic GMP-AMP synthase inhibitorsJ. Org. Chem.85(3)1579-1600(2020)

Polyinosinic-polycytidylic acid potassium (Poly(I:C) potassium), a synthetic double-stranded RNA analog, serves as an agonist for toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I (RIG-I)-like receptors (RIG-I and MDA5), offering applications in immunotherapy. Its sodium variant enhances both innate and adaptive immune responses when used as a vaccine adjuvant and is instrumental in modifying the tumor microenvironment. Additionally, Poly(I:C) potassium can directly induce apoptosis in cancer cells [1] [2] [3].

Poly(I:C):Kanamycin (1:1) sodium is a complex.Poly(I:C) is a synthetic double-stranded RNA analogue and a TLR3 and RIG-I/MDA5 agonist that enhances immunity and promotes apoptosis in cancer cells.Kanamycin is an antimicrobial agent that is effective against both Gram-negative and positive bacteria which is able to bind the 70S ribosomal subunit.

Antiviral agent 35 (compound 4d) is a potent oral inhibitor of the influenza virus, targeting early stages of viral replication. It suppresses influenza-induced ROS accumulation, autophagy, apoptosis, and the inflammatory response mediated by the RIG-1 pathway in a mouse model of pulmonary infection. Its cytotoxicity is minimal in MDCK cells, with a CC50 greater than 800 μM, and it has anti-H1N1 (A Weiss 43) activity with an EC50 of 2.28 μM [1].