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STING agonists and inhibitors act on an adaptor protein of the cytosolic DNA sensing pathway. Stimulator of interferon genes (STING) was described in 2008 as an endoplasmic reticulum adaptor needed for innate immune signaling and type I interferon induction. STING binds cyclic dinucleotides directly, both bacterial molecules such as cyclic di-GMP and the mammalian second messenger made by cyclic GMP-AMP synthase (cGAS) once it detects cytosolic DNA. Agonists listed here include 2',3'-cGAMP, Cyclic-di-GMP, ADU-S100 disodium salt (MIW815 disodium salt) and numbered compounds such as STING agonist-1. Inhibitors include H-151 and the mouse-directed C-176 and C-178, which belong to a class of covalent compounds that modify a cysteine of the transmembrane region.
C-178, a covalent inhibitor of STING, binds to Cys91, potently and selectively suppresses the STING responses elicited by distinct bona fide activators in mouse but not human.
STING-IN-17 is a potent inhibitor of STING (Stimulator of Interferon Genes), with human STING IC50 of 29 nM and mouse STING IC50 of 15 nM. This compound effectively inhibits the phosphorylation of STING, TBK1, and IRF3, leading to a dose-dependent reduction in the mRNA expression of key inflammatory markers such as IP10, IFNB1, and ISG56. STING-IN-17 also decreases reactive oxygen species (ROS) levels and inhibits the activation of apoptosis-related proteins cleaved-PARP and caspase-3. Its potential applications make it valuable for research into inflammatory conditions, particularly acute kidney injury.
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STING-IN-16 is a potent inhibitor of the Stimulator of Interferon Genes (STING) pathway, exhibiting IC50 values of 44 nM in human cells and 32 nM in murine cells. It effectively inhibits STING activation, leading to restoration of renal mitochondrial function, reduction of reactive oxygen species (ROS) production, and decreased cell apoptosis. With demonstrated anti-inflammatory efficacy in vivo, STING-IN-16 is valuable for research focused on autoimmune and autoinflammatory diseases.
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STING-IN-11 is a potent STING inhibitor with an IC50 of 37.8 nM. By blocking the palmitoylation of the STING protein, it effectively inhibits STING-mediated downstream signaling and associated inflammatory pathways. This compound demonstrates favorable in vivo safety, making it an excellent candidate for research into STING-related inflammatory and autoimmune diseases.
SN-011 is a selective inhibitor of the STING pathway, displaying an IC50 of 76 nM. By competing with cyclic dinucleotides (CDNs) for the binding site on the STING dimer, SN-011 effectively prevents CDN binding and subsequent STING activation. This compound is valuable for investigating STING-mediated autoimmune and inflammatory diseases, offering insights into therapeutic strategies targeting this critical signaling pathway.
STING-IN-2 is a potent covalent inhibitor of Stimulator of Interferon Genes (STING), effectively targeting both mouse and human STING isoforms. This compound is instrumental in studying the role of STING in autoinflammatory diseases, facilitating the exploration of therapeutic interventions. Its ability to modulate STING activity makes it a valuable tool for researchers investigating immune response and signaling pathways.
LB244 is a STING inhibitor that functions by modulating the STING signaling pathway to reduce inflammation. It exhibits a potent inhibitory effect (EC50 = 0.8 μM) on STING-dependent inflammatory responses. While LB244 shows promising potential in preclinical studies, its pharmacokinetic profile suggests limited oral bioavailability in murine models. This compound is suitable for research applications focused on understanding STING-related inflammatory disorders.
STING-IN-3 is a potent inhibitor of the stimulator of interferon genes (STING), specifically targeting both human and murine STING. It covalently modifies the conserved transmembrane cysteine residue at position 91, effectively preventing activation-induced palmitoylation. This activity provides valuable utility in research applications exploring STING-related pathways in immune response and therapeutic interventions in autoimmune diseases and cancer.
SN-001 is a selective inhibitor of the STING (Stimulator of Interferon Genes) pathway, exhibiting an IC50 of 3.82 μM. This compound is valuable for investigating the role of STING in immune responses and inflammatory diseases. Its inhibitory activity allows for the evaluation of STING's effects on cytokine production and other immune-related pathways, making it a useful tool for research in immunology and drug development.
STING-IN-4 is a potent STING inhibitor that effectively reduces the expression and activation of STING and nuclear factor-κB (NF-κB) signaling pathways. This compound exhibits significant anti-inflammatory activity, making it a valuable tool for investigating sepsis and related inflammatory conditions. Researchers can utilize STING-IN-4 to explore the therapeutic potential of modulating STING activity in various biological contexts.
STING antagonist-2 is a potent inhibitor of the Stimulator of Interferon Genes (STING), exhibiting a pIC50 of 8.9. This compound is primarily utilized in immunity research to investigate the modulation of STING-mediated immune responses. Its application extends to studies focused on immune evasion and potential therapeutic approaches in autoimmune disorders.
STING-IN-7 is a potent inhibitor of the Stimulator of Interferon Genes (STING) pathway, demonstrating an IC50 of 11.5 nM. This compound effectively inhibits the phosphorylation of STING, interferon regulatory factor 3 (IRF3), and TANK-binding kinase 1 (TBK1). STING-IN-7 is valuable for investigating the role of STING modulation in autoimmune and inflammatory disease research.
SB24011 is a selective STING modulator that inhibits the TRIM29-STING protein-protein interaction. By binding to STING, it effectively prevents TRIM29-induced K48-linked ubiquitination, leading to an increase in intracellular STING protein levels. This compound promotes the expression of inflammatory cytokines and enhances STING-mediated immune responses, demonstrating abscopal antitumor activity that stimulates tumor regression and T cell infiltration. SB24011 is particularly relevant for research on colon cancer and melanoma, showing potential synergy when used in conjunction with STING agonists or anti-PD1 antibodies.
STING-IN-15 is a potent STING inhibitor that exhibits an IC50 of 116 nM against human STING and 96.3 nM against mouse STING. It effectively disrupts the STING signaling pathway in cellular models, leading to a decrease in the secretion of IFN-β and IP-10, and downregulating the expression of key inflammatory markers such as ISG15, ISG56, and TNF-α. Additionally, STING-IN-15 shows promise in reducing systemic and renal inflammation triggered by STING agonists in murine models, thereby mitigating tissue damage and the overexpression of interferon-related genes. This compound is valuable for research into acute kidney injury and various autoimmune/inflammatory diseases.
H-151 Alkyne is a selective inhibitor of STING (Stimulator of Interferon Genes). This compound demonstrates potential for modulating immune responses, making it valuable in the study of autoimmune diseases such as systemic lupus erythematosus and scleroderma, as well as autoinflammatory conditions. Its ability to interfere with STING pathways allows researchers to explore therapeutic strategies targeting these diseases.
STING-IN-5 is a potent inhibitor of the STING pathway, specifically targeting the STING protein to attenuate LPS-induced nitric oxide synthesis in macrophages, with an IC50 value of 1.15 μM. This compound effectively reduces inflammatory responses, making it valuable for research focused on anti-inflammatory diseases and sepsis. Its ability to modulate immune responses highlights its potential in elucidating the role of STING in various pathological contexts.
STING modulator-4 (compound AIH05) is a competitive modulator of the Stimulator of Interferon Genes (STING), exhibiting a Ki of 0.0933 μM for the R232H variant of STING. This compound demonstrates biological activity with an EC50 value exceeding 10 μM for phosphorylated IRF3 in THP-1 cells. STING modulator-4 is significant for research in immunology and enhances understanding of STING-mediated signaling pathways.
STING-IN-14 is a potent STING inhibitor with an IC50 value of 0.6 nM. This compound effectively suppresses the activation of the IRF pathway in THP1-DualTM cells, making it a valuable tool for studying the role of STING in immune responses. STING-IN-14 is particularly relevant for research focused on autoimmune diseases, contributing to a better understanding of disease mechanisms and potential therapeutic interventions.
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STING modulator-5 is an inhibitor of the stimulator of interferon genes (STING) pathway, displaying a pIC50 value of 9.5. This compound effectively antagonizes peripheral blood mononuclear cells (PBMC) with a pIC50 of 8.1 and demonstrates activity against THP-1 cells. STING modulator-5 is a valuable tool for studying immunological diseases and exploring therapeutic avenues targeting STING-related signaling pathways.
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STING modulator-3 is a selective STING inhibitor that targets the R232 variant of STING, exhibiting an inhibition constant (Ki) of 43.1 nM in scintillation proximity assays. This compound does not influence IRF-3 activation or TNF-β induction in THP-1 cells, making it a valuable tool for studying STING-mediated signaling pathways and their implications in immune responses and inflammatory diseases. Its specificity and potency provide researchers with a resource for exploring STING-related mechanisms in various biological contexts.
Synonyms: NSC 335504
Clonixeril (NSC 335504) is a non-nucleotide modulator of human STING (hSTING), exhibiting a unique dual mechanism of action. It acts as a weak agonist at micromolar concentrations while demonstrating antagonistic properties of the hSTINGWT pathway at low femtomolar and attomolar levels. Clonixeril effectively reduces hSTING oligomerization, proving useful in elucidating the complexities of STING signaling and its role in immune responses. This compound serves as a valuable tool for research in immunology and drug discovery targeting STING-related pathways.
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STING modulator-7 is a potent modulator of the stimulator of interferon genes (STING), enhancing the signaling pathway associated with innate immune responses. This compound exhibits significant biological activity in activating STING-dependent pathways, promoting type I interferon production and immune cell activation. It is primarily utilized in research applications focused on cancer immunotherapy, infectious disease models, and studies of immune system regulation.
Synonyms: Stimulator of interferon genes 18
STING18 is a small molecule inhibitor targeting the STING (Stimulator of Interferon Genes) protein. It exhibits effective inhibition of STING-mediated cytokine release and demonstrates favorable oral bioavailability with slow binding kinetics. This compound is valuable for research applications focused on immune modulation and the study of STING-related signaling pathways.
