STING Activator

Cyclic-di-GMP is a STING agonist and a bacterial second messenger that coordinates different aspects of bacterial growth and behavior, including motility, virulence, biofilm formation, and cell cycle progression. Cyclic-di-GMP has anti-cancer cell proliferation activity and also induces elevated CD4 receptor expression and cell cycle arrest. Cyclic-di-GMP can be used in cancer research.

2'2'-cGAMP disodium, a synthetic CDN, binds STING in the immune response, inducing IFN-β. 2'2'-cGAMP disodium binds weaker binding to STING than 2'3'-cGAMP (HY-100564) but stronger than other CDNs.

dsVACV-70mer (sodium) is a 70 bp double-stranded oligonucleotide containing viral DNA motifs derived from vaccinia virus DNA. dsVACV-70mer (sodium) has potently induces IFN-β via a STING-dependent manner.

Biotin-labeled ISD sodium is a biotin-labeled form of ISD sodium (HY-160225). ISD sodium is an interferon-stimulatory DNA, a 45 bp non-CpG double-stranded oligonucleotide derived from the Listeria monocytogenes genome. ISD sodium can potently induce type I interferon production via the cGAS‑STING‑TBK1‑IRF3 pathway.

HSV-60mer sodium is a 60 bp double-stranded DNA oligonucleotide derived from the HSV-1 genome, and also an IFNβ inducer. HSV-60mer sodium colocalizes with endogenous cytoplasmic IFI16 in immune cells. HSV-60mer sodium activates the transcription factors IRF3 and NF-κB, induces the production of proinflammatory cytokines, and inhibits HSV-1 replication in immune cells. HSV-60mer sodium can be used in studies related to herpes simplex virus type 1 infection.

KAS 08 is an effective STING pathway activator in vitro and in vivo. KAS 08 enhances STING activity initiated by cGAMP.

PDIC-DPC is a HMGA1 inhibitor and lung-targeting agent. PDIC-DPC upregulates STING expression and enhances STING-mediated immune signaling. PDIC-DPC inhibits the TGFβ-Smad pathway and activates AMPK. PDIC-DPC forms nanocomplexes with fibrinogen β chain and vitronectin, and achieves lung-specific accumulation by binding to pulmonary endothelial receptors. PDIC-DPC reverses established pulmonary fibrosis, reduces collagen deposition, restores alveolar structure, improves pulmonary function, and inhibits in situ ESCC growth. PDIC-DPC can be used for the research of esophageal squamous cell carcinoma and idiopathic pulmonary fibrosis.

¹³C20,¹⁵N10-Cyclic di-GMP (¹³C20,¹⁵N10-c-di-GMP) is ¹³C and ¹⁵N labeled Cyclic-di-GMP (disodium). Cyclic-di-GMP disodium is a STING agonist and a bacterial second messenger that coordinates different aspects of bacterial growth and behavior, including motility, virulence, biofilm formation, and cell cycle progression. Cyclic-di-GMP disodium has anti-cancer cell proliferation activity and also induces elevated CD4 receptor expression and cell cycle arrest. Cyclic-di-GMP disodium can be used in cancer research.

Enpp-1-IN-25 (Compound 30) is an ENPP1 inhibitor with an IC₅₀ of 8.05 nM and low oral bioavailability. Enpp-1-IN-25 can effectively activate the intracellular STING pathway by inhibiting cGAMP degradation. Enpp-1-IN-25 can enhance immune cell infiltration in the tumor microenvironment and type I interferon responses, and potentiate the antitumor efficacy of the anti-PD-L1 antibody. Enpp-1-IN-25 can be used in the research of cancer immunotherapy.

SC13 is an orally active, selective Flap structure-specific endonuclease 1 (FEN1) inhibitor and mu opioid receptor (MOR) activator. SC13 impairs DNA damage repair and induces apoptosis in cancer cells. SC13 activates cGAS-STING signaling, increases chemokine secretion, and promotes CAR-T cell infiltration at solid tumour sites. SC13 can be used for the research of solid tumours and pain.

NA-Ir is a Ferroptosis inducer. NA-Ir targets mitochondrial DNA (mtDNA) and activates the cGAS-STING pathway to induce ferritinophagy (Autophagy), while also generating reactive oxygen species (ROS) through photodynamic therapy (PDT), depleting glutathione (GSH), and downregulating glutathione peroxidase 4 (GPX4), thereby triggering lipid peroxidation and Ferroptosis. NA-Ir exhibits higher anticancer activity under light exposure and selectively inhibits cancer cells with high H₂S levels.

STING agonist-11 (Compound 92) is a potent small molecule cyclic urea activator of STING with EC₅₀ of 18 nM. Activation of STING is a highly promising approach in immunotherapy.

MT-44 is a highly selective and potent mTOR inhibitor with an IC₅₀ of 49.4 nM. MT-44 can inhibit cancer cells proliferation, migration and invasion. MT-44 can induce cells apoptosis and ROS production and cause G2/M phase arrest. MT-44 can activate the cGAS/STING pathway. MT-44 can be used for the research of cancer, such as triple-negative breast cancer.

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.

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 (HY-100564) but stronger than other CDNs.

Enpp-1-IN-32 is an orally active, selective ENPP-1 inhibitor with an IC₅₀ of 9.5 nM. Enpp-1-IN-32 shows selectivity over ENPP2/ENPP3. Enpp-1-IN-32 blocks cGAMP hydrolysis, and activates the STING pathway. Enpp-1-IN-32 exhibits antitumor effects in syngeneic mouse models. Enpp-1-IN-32 can be used for the research of triple-negative breast carcinoma.

Enpp-1-IN-27 is a selective ENPP1 inhibitor with an IC₅₀ of 14.68 nM, exhibiting approximately 410-fold selectivity against ENPP2 and 10-fold selectivity against ENPP3. Enpp-1-IN-27 stabilizes cGAMP levels and activates the STING pathway, promoting cytokine release and enhancing innate immune responses. Enpp-1-IN-27 induces ISRE activation and amplified cGAMP-mediated immune responses and shows the desired antitumor efficacy in the 4T1 and CT26 syngeneic mouse models. Enpp-1-IN-27 can used for the studies of breast cancer and colon cancer.

SMU-3k is a STING activator and PD-L1 inhibitor, with a PD-L1 IC₅₀ of 106 nM, a K_D of 386 nM for human PD-L1, and a K_D of 352 nM for murine PD-L1. SMU-3k activates the STING pathway, induces phosphorylation of TBK1 and IRF3, and promotes the expression of IFN-β, IL-6 and CXCL10. SMU-3k blocks the PD-1/PD-L1 interaction, reduces PD-L1 levels and induces PD-L1 internalization. Through dual immunomodulation, SMU-3k exerts synergistic tumor growth inhibitory effects in a mouse colon cancer model. SMU-3k can be used for the research of colon cancer.

SH-273 is a dual targeting compound. SH-273 has dual function to stimulate STING function (EC₅₀: 100 nM) and inhibits PI3Kγ (IC₅₀: 7 nM). SH-273 can be used in the research of pancreatic cancer.

Telomeric G4s ligand 2 is an orally active, selective ligand of telomeric G-quadruplex (G4), with an IC₅₀ of 0.4 μM. Telomeric G4s ligand 2 binds to dimeric telomeric G4, inhibits the activities of DHX36 and BLM helicases. Telomeric G4s ligand 2 activates cGAS-STING and TERRA-ZBP1 pathways, inducing autophagy and G2/M cell cycle arrest, and exhibits antiproliferative effects across cancer cell lines. Telomeric G4s ligand 2 can be used for the study of colorectal cancer.