PDIC-NN dimethanesulfonate (PDIC-NS) is a STING activator with anticancer activity. PDIC-NN dimethanesulfonate promotes the content and biostability of endogenous cyclic dinucleotides (CDNs). PDIC-NN dimethanesulfonate triggers ROS burst and causes serious damage to mitochondria. PDIC-NN dimethanesulfonate induces cell apoptosis and inhibits DNA replication. PDIC-NN dimethanesulfonate activates cGAS-STING signaling pathway, enhances the immunogenicity of tumor cells and activates a robust innate immune response.

3'2'-cGAMP (c[A(2',5')pG(3',5')p]) disodium is the disodium of 3'2'-cGAMP). 3'2'-cGAMP (c[A(2',5')pG(3',5')p]) is a cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) isomer. 3'2'-cGAMP exhibits high selectivity for Drosophila STING (dSTING), activating the dSTING-NF-κB signaling pathway, inducing the expression of Sting-regulated genes (Srg) and conferring a potent antiviral state in vivo. 3'2'-cGAMP is resistant to cleavage by viral poxins. 3'2'-cGAMP can be used for the study of viral infections.

3'2'-cGAMP (c[A(2',5')pG(3',5')p]) is a cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) isomer. 3'2'-cGAMP exhibits high selectivity for Drosophila STING (dSTING), activating the dSTING-NF-κB signaling pathway, inducing the expression of Sting-regulated genes (Srg) and conferring a potent antiviral state in vivo. 3'2'-cGAMP is resistant to cleavage by viral poxins. 3'2'-cGAMP can be used for the study of viral infections.

H-151 Alkyne (Compound H-151-AL) is a selective STING (Stimulator of interferon genes) inhibitor. H-151 Alkyne is promising for research of autoimmune diseases such as systemic lupus erythematosus, scleroderma, and autoinflammatory diseases.

diABZI-Mal is a STING agonist. diABZI-Mal activates cGAS-STING pathway to induce cytokine production such as interferon-type I. diABZI-Mal promotes maturation of DC cells and efficiently induces CD8+ T immune reaction. diABZI-Mal inhibits tumor growth.

Clonixeril (NSC 335504) is a non-nucleotide hSTING modulator. Clonixeril has weak agonist activity at micromolar concentrations and results in antagonism of the hSTINGWT pathway at low femtomolar (10-15 M) and in some cases even attomolar (10-18 M) concentrations. Clonixeril reduces hSTING oligomerization at a concentration of 1 aM-1 pM.

INI3069 is a selective human stimulator of interferon gene (STING) agonist. INI3069 is promising for research of cancers.

(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 a key amide benzimidazole (ABZI) component and shows reproducible inhibition of 3H-cGAMP binding to STING with an apparent inhibition constant IC50 of 14 μM. (S)-2-(1-Ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1-(2-hydroxy-2-phenylethyl)-1H-benzo[d]imidazole-5-carboxamide can be used for tumor research.

Parent CDN is a cyclic dinucleotide and a STING agonist. Parent CDN exhibits anti-tumor activity.

3’,5’-DiOA-dC is a hydrophobic nucleotide lipid and a ligand for the STING agonist c-di-GMP (CDG). 3’,5’-DiOA-dC can assemble with CDG and form stable cyclic dinucleotide nanoparticles via various supramolecular forces driven by molecular recognition. 3’,5’-DiOA-dC can decrease tumor weight and volume, increase CD8 T cell, neutrophils as well as NK cell counts in tumor microenvironment in combination with CDG. 3’,5’-DiOA-dC also increases the levels of TNF-α and IFN-γ in murine melanoma model.

BMS-025 is a orthosteric STING agonist. BMS-025 can induces chemical shift of STING M271 residue, further activating STING IFN signaling. BMS-025 can be used for monogenic autoinflammatory disease like SAVI disease research.

endo-S-cGAFMP (Compound 3) is a STING agonist. endo-S-cGAFMP induces the production of interferon regulatory factors and proinflammatory cytokines by activating the cGAS-STING pathway, thereby enhancing innate and adaptive immune responses. endo-S-cGAFMP has potent immunostimulatory capacity in THP1 monocytes and RAW macrophages (EC50 values of 2.45 μM and 5.54 μM, respectively). endo-S-cGAFMP has significant antitumor activity. endo-S-cGAFMP can be used as a potential cancer immunotherapeutic agent, especially for studies of systemic administration.

ZSA-215 is a potent and orally active STING agonist with an EC50 of 3.3 μM. ZSA-215 enhances STING signaling through promoting the phosphorylation of STING and interferon regulatory factor 3 (IRF3) and secretion of IFN-β. ZSA-215 inhibits tumor regression and long-term survival of mice in MC38 colon cancer model. ZSA-215 can be used to the study of colon cancerr.

diABZI-i is a orthosteric STING inhibitor. diABZI-i significantly inhibits cGAMP-induced IFNβ in PBMCs with an IC50 of 49 nM. diABZI-i also activates V155M SAVI constitutive signaling in STING V155M THP-1 cells model with potent agonism (EC50: 17  nM). diABZI-i can be used for monogenic autoinflammatory disease like SAVI disease research.

diABZI-a1 is a orthosteric STING agonist with EC50 of 117 nM for IFNβ in human PBMCs. diABZI-a1 can be used for monogenic autoinflammatory disease like SAVI disease research.

ZSA-51 is a potent and orally active STING agonist. ZSA-51 shows anticancer activity. ZSA-51 remodeles immune microenvironment both in tumor and lymph node.

VB-85247 is a STING agonist. VB-85247 induces upregulation of inflammatory cytokines IFNα/β, TNFα, IL6, and CXCL10, as well as maturation and activation of dendritic cells by activating the STING pathway. VB-85247 can achieve regression of intrabladder tumors and can be used in bladder cancer research.

PDIC-NN is an intermediate in the synthesis of PDIC-NS. PDIC-NS is a STING activator with anticancer activity.

PDIC-NC is a STING agonist. PDIC-NC is cytotoxic to tumor cells and induces ROS explosion, apoptosis and autophagy. PDIC-NC has lung specific distribution and can be used in the study of lung cancer.

M04 is an agonist of STING. It induces the expression of the IFN reporter gene in HEK293T cells expressing wild-type human STING, but does not induce this expression in HEK293T cells expressing the R71H-G230A-R293Q (HAQ) STING variant or in mouse RAW 264.7 cells, indicating that its activity is dependent on allelic and species variations. M04 induces the production of TNF-α, IL-10, IL-1β, and IL-12p70 in human peripheral blood mononuclear cells (PBMCs). At a concentration of 50 µM, M04 stimulates dendritic cells isolated from PBMCs to express the MHC class II cell surface receptor HLA-DR and co-stimulatory molecules CD40, CD80, and CD86, and also enhances their ability to activate T cells in an ex vivo assay. M04 can be used in research on inflammatory immune diseases.

GHN105 is an orally active inhibitor for STING that inhibits STING-dependent IFN-β secretion in THP-1 human monocytes with an IC50 of 4.4 μM. GHN105 reduces the IFN-β, IL-6 and CXCL10 levels in serum, and alleviates colitis in DSS.

BDW-OH is an active metabolite of BDW568. 2-Methylbiphenyl-oxadiazole-NH-Ph-NH-PEG3-C2-NH-Boc can be utilized in AUTAC synthesis.

2'2'-cGAMP, a synthetic CDN, binds STING in the immune response, inducing IFN-β. 2'2'-cGAMP binds weaker binding to STING than 2'3'-cGAMP. Emavusertib tosylate is an orally active inhibitor for IRAK4 (IC50=57 nM) and FLT3. Emavusertib tosylate inhibits NF-κB and MyD88 signaling pathways, reduces the generation of pro-inflammatory cytokines like IL-6 and IL-10, thereby exhibiting anti-inflammatory and anti-proliferative activities against cancer cells, leading to cell apoptosis. Emavusertib tosylate exhibits antitumor activity in mouse model.

SR-717 is a non-nucleotide STING agonist with EC50s of 2.1 μM and 2.2 μM in ISG-THP1 (WT) and ISG-THP1 cGAS KO (cGAS KO) cell lines, respectively. SR-717 is a stable cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) mimetic.

H-151(H151) is a novel STING (stimulator of interferon genes) antagonist.

STING agonist-7 is a non-nucleotide STING agonist. STING agonist-7 binds selectively to mouse STING but not human STING. STING agonist-7 penetrates cell membrane poorly.

diABZI STING agonist-1 is a selective stimulator of interferon genes (STING) receptor agonist, with EC50s of 130, 186 nM for human and mouse, respectively.

cGAMP (Cyclic GMP-AMPP) diammonium functions as an endogenous second messenger in metazoans and triggers interferon production in response to cytosolic DNA. cGAMP diammonium activates stimulator of interferon genes (STING), which activates a signaling cascade leading to the production of type I interferons and other immune mediators.

3’3’-cGAMP Fluorinated (c-[2'FdGMP]-[2'FdAMP]) is a synthetic analog of cyclic guanosine monophosphate- adenosine monophosphate (cyclic GMP-AMP, cGAMP) with a fluorine atom at 2’ position of the nucleosides. 3’3’-cGAMP is a cyclic di-nucleotide produced by bacteria. It is also referred to as "canonical" cGAMP due the presence of the classical 3’-5’ phosphodiester linkages between the guanosine and the adenosine. It has been reported that cGAMP binds STING (stimulator of IFN genes) and subsequently induces TBK1-IRF3-dependent production of IFN-β [1]. The incorporation of fluorine into biologically active molecules is commonly used in medicinal chemistry to improve their metabolic stability or to modulate physicochemical properties such as lipophilicity [2, 3]. Moreover, the introduction of a fluorine atom can change the biological activities of a molecule. Interestingly, when used at low concentrations in various cellular assays, 3’3’-cGAMP Fluorinated induces higher levels of type I IFNs than does cGAMP. STING ligands such as cGAMP induce type I IFNs and activate interferon stimulated genes (ISG) through IRFs. To facilitate their study, InvivoGen has developed stable reporter cells in two well established immune cell models: THP-1 human monocytes and RAW 264.7 murine macrophages. These cells express a reporter gene (SEAP or Lucia luciferase), under control of an IRF-inducible promoter.

SHR1032 is a novel small molecule non-cyclic di-nucleotide STING agonist, exhibits significantly high affinity binding to STING and cellular reporter assay (EC50=30 nM).