interferon a 1

CAY10748 is an agonist of stimulator of interferon genes (STING; IC50= 0.3794 μM in a competition binding assay).1It activates STING in STING-expressing, but not STING knockout, THP-1 cells (EC50s = 0.287 and >100 μM, respectively, in a reporter assay). It induces phosphorylation of STING at the serine in position 366, as well as phosphorylation of TBK1 and IFN regulatory factor 3 (IRF3), indicating activation of the STING-TBK1-IRF3 signaling pathway. CAY10748 increases the secretion of IFN-β and the levels of chemokine (C-X-C motif) ligand 10 (CXCL10), and IL-6 in peripheral blood mononuclear cells (PBMCs) when used at a concentration of 10 μM. It also reduces tumor growth in a CT26 murine colon cancer model when administered at a dose of 0.15, but not 1.5, mg/kg. 1.Xi, Q., Wang, M., Jia, W., et al.Design, synthesis, and biological evaluation of amidobenzimidazole derivatives as stimulator of interferon genes (STING) receptor agonistsJ. Med. Chem.63(1)260-282(2019)

STING agonist C11 is an agonist of the stimulator of interferon genes (STING) pathway.1 It induces secretion of type I IFN from THF and MM6 cells when used at a concentration of 50 μM. STING agonist C11 induces phosphorylation of IFN regulatory factor 3 (IRF3) and increases expression of IFIT1 and viperin, but not IL-1β, IL-6, or IL-8 in THF cells in a STING-dependent manner. It reduces viral titers of chikungunya, Venezuelan equine encephalitis, o'nyong-nyong, Mayaro, and Ross River viruses grown in THF cells (EC90s = 16.44, 16.7, 18.84, 25.19, and 22.57 μM, respectively), an effect that is dependent on the presence of STING and the IFN-α/β receptor (IFNAR).References1. Gall, B., Pryke, K., Abraham, J., et al. Emerging alphaviruses are sensitive to cellular states induced by a novel small-molecule agonist of the STING pathway. J. Virol. 92(6), e01913-01917 (2018). STING agonist C11 is an agonist of the stimulator of interferon genes (STING) pathway.1 It induces secretion of type I IFN from THF and MM6 cells when used at a concentration of 50 μM. STING agonist C11 induces phosphorylation of IFN regulatory factor 3 (IRF3) and increases expression of IFIT1 and viperin, but not IL-1β, IL-6, or IL-8 in THF cells in a STING-dependent manner. It reduces viral titers of chikungunya, Venezuelan equine encephalitis, o'nyong-nyong, Mayaro, and Ross River viruses grown in THF cells (EC90s = 16.44, 16.7, 18.84, 25.19, and 22.57 μM, respectively), an effect that is dependent on the presence of STING and the IFN-α/β receptor (IFNAR). References1. Gall, B., Pryke, K., Abraham, J., et al. Emerging alphaviruses are sensitive to cellular states induced by a novel small-molecule agonist of the STING pathway. J. Virol. 92(6), e01913-01917 (2018).

STING Agonist-13, a stimulator of interferon genes (STING) agonist, enhances cancer immunity through STING-mediated immune activation. It activates STING downstream signaling to promote type I interferon immune responses, significantly reduces tumor volume, and exhibits immunological memory-derived cancer inhibition [1].

STING-IN-5, a potent inhibitor of the Stimulator of Interferon Genes (STING) pathway, significantly suppresses lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis in macrophages, exhibiting an IC50 of 1.15 μM. This compound dampens the inflammatory response and offers potential for research into anti-inflammatory diseases and sepsis [1].

Dazostinag (TAK-676 free base) is a stimulator of interferon genes (STING) protein agonist with antineoplastic properties and serves as a payload for the synthesis of antibody-drug conjugates (ADCs) [1] [2].

Cepeginterferon alfa-2b, a pegylated interferon, features a polyethylene glycol (PEG) base with a molecular weight of 20 kDa. This compound is utilized in the research of numerous diseases, including hepatitis C virus (HCV), polycythemia vera (PV), and essential thrombocythemia (ET) [1] [2].

Interferon alfa, a type I interferon, activates new genes, displaying strong antiviral and antiproliferative effects on target cells. It signals through receptor-mediated activation of Stat1 and Stat2, which heterodimerize into a STAT complex binding with the DNA-binding protein IRF-9 (p48) to form ISGF-3 (IFN-stimulated gene factor 3). This complex further activates driver genes to fulfill its antiviral role [1].

STING-IN-7 (compound 21) is a potent inhibitor of the stimulator of interferon genes (STING) pathway, with an inhibitory concentration (IC50) of 11.5 nM, effectively hampering the phosphorylation of both STING and interferon regulatory factor 3 (IRF3) [1].

Peginterferon alfa-2b (Sch 54031), a recombinant alfa-2b interferon covalently bonded to polyethylene glycol (PEG), acts as an immunomodulator. This compound is effective in reducing viral DNA in HIV and has potential applications in melanoma research [1] [2].

CDN-A, a cyclic di-nucleotide, serves as a precursor for synthesizing antibody-drug conjugates (ADC) and acts as a potent stimulator of both innate and adaptive immune responses. In humans, these cyclic di-nucleotides, produced endogenously in response to foreign DNA or by bacterial pathogens, activate the innate immune system by inducing the expression of interferon genes [1] [2] [3].

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)

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-22 (CF501) is a potent non-nucleotide STING agonist that functions as an adjuvant by activating STING to induce the type I interferon (IFN-I) response and the production of proinflammatory cytokines. It enhances the efficacy of original protein vaccines by providing potent, broad, and long-term immune protection. Additionally, STING Agonist-22 has applications in research on SARS-CoV-2 variants and sarbecovirus diseases [1].

93-O17S is a chalcogen-containing cationic lipidoid. It 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 utilized 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.

BI 7446 is a potent and selective cyclic dinucleotide (CDN)-based stimulator of interferon genes (STING) agonist capable of activating all five STING variants in cells, thus inducing tumor-specific immune-mediated tumor rejection. This compound is utilized in immuno-oncology research [1].

QL-1200186 is an orally active, selective TYK2 inhibitor that, upon dose-dependent oral administration, suppresses interferon-γ (IFNγ) production following interleukin-12 (IL-12) stimulation and markedly improves skin lesions in a psoriatic mouse model [1].

STING agonist 12L is a stimulator of interferon genes (STING) agonist that exhibits binding affinity for both wild-type STING and its variants R232, AQ, and Q with half-maximal inhibitory concentrations (IC50s) of 1.15 µM for wild-type, 1.06 µM for R232, 0.61 µM for AQ, and 1.12 µM for Q. It effectively induces reporter gene expression in THP-1 and RAW 264.7 cells, with half-maximal effective concentrations (EC50s) of 0.38 µM and 12.94 µM, respectively. At a concentration of 5 µM, STING agonist 12L escalates the expression of IFNB1, CXCL10, and IL6 mRNA in THP-1 cells. When administered in vivo at a dose of 10 mg/kg, it enhances plasma IFN-β levels and considerably reduces tumor volume and the number of lung metastases in a B16/F10 murine melanoma model.

GSK-2245035 maleate is a selective Toll-like receptor 7 (TLR7) agonist with preferential Type-1 interferon (IFN)-stimulating properties.

PD-1 PD-L1-IN 6 (compound A13) is a potent inhibitor of PD-1 PD-L1 interaction (IC50 = 132.8 nM) with outstanding immunoregulatory activity. In a Hep3B OS-8 hPD-L1 and CD3 T cell co-culture model, PD-1 PD-L1-IN 6 significantly elevates interferon-γ secretion without significant toxic effects. Additionally, in a T cell-tumor co-culture model, PD-1 PD-L1-IN 6 restores the immune response.

CL845, a STING (stimulator of interferon genes) agonist analog to CL656, is instrumental in synthesizing conjugatable PRR (pattern recognition receptor) ligands aimed at targeting STING. It holds potential applications in researching cancers, immunological disorders, or infections [1].

Ezabenlimab (BI-754091) is an anti-PD-1 monoclonal antibody (mAb) with a binding constant (Kd) of 6 nM in CHO cells. It inhibits the interaction between PD-1 and its ligands, PD-L1 and PD-L2, enhances interferon-γ secretion in T cells, and inhibits tumor growth in vivo [1].

Dazukibart is a humanized IgG1κ monoclonal antibody of murine origin, specifically targeting interferon beta 1 (IFNB1) [1].

Albinterferon alfa-2B (alb-IFN), a recombinant protein, comprises interferon alfa-2b conjugated to human albumin and is utilized in the study of chronic hepatitis C [1].