sting in 2

STING-IN-2 (C-170) is a potent, covalent inhibitor of STING, effectively targeting both mouse (mmSTING) and human STING (hsSTING), and is applicable for autoinflammatory disease research.

STING ligand-2 serves as a ligand for STING and can be utilized as the target protein ligand in the synthesis of the PROTAC degrader STING-IN-10.

STINGDegrader-2 (Compound SI-43) is an inhibitor and mutant-specific degrader of STING. It effectively suppresses cGAMP-induced STING activation and significantly reduces the release of IFN-β and CXCL-10. By binding to two pockets of the STING dimer, it inhibits activity and induces proteasome-independent degradation of the mutant STINGS154 and STINGM155 (DC50 values of 0.31 and 0.76 μM, respectively). STINGDegrader-2 is applicable in the study of STING-related autoimmune diseases.

PROTAC STING Degrader-2 is a protein degrader targeting the Stimulator of interferon genes (STING) with a DC50 of 0.53 μM. It induces STING protein degradation by covalently binding to both the STING protein and an E3 ubiquitin ligase. This compound is useful for studying the role of STING in autoinflammatory and autoimmune diseases.

STINGagonist-49-PAB-Ala-Val-CO-C2-mal is a peptide-cSTING linker-payload, used as a Drug-Linker Conjugate for ADC (Antibody-Drug Conjugate). It serves as a component for ADC synthesis.

STINGagonist-49-β-D-Glu-benzylalcohol-di(amide-C2)-mal (compound gluc-cSTING linker-payload) is a drug-linker conjugate used in antibody-drug conjugates (ADC). STINGagonist-49-PAB-Ala-Val-CO-C2-mal is applicable for ADC synthesis.

STINGagonist-49-CO-C2-mal-Cys (compound 2) is a derivative of STINGagonist-49-CO-C2-mal, resulting from the metabolism and payload release of an ADC, and exhibits antitumor activity in vivo.

STINGagonist-49-CO-C2-mal (compound ncSTING linker-payload) is a non-cleavable Drug-Linker Conjugate for ADC (Antibody-Drug Conjugates). This compound is used in the synthesis of ADCs.

STING agonist-20-Ala-amide-PEG2-C2-NH2, an active scaffolding molecule, engages the stimulator of interferon genes (STING) pathway and is used in the synthesis of immune-stimulating antibody conjugates (ISAC), particularly in cancer research [1].

STING Agonist-20-Ala-amide-PEG2-C2-NH2 (Compound 30b) TFA, an active compound that interacts with the stimulator of interferon genes (STING), is utilized in the synthesis of immune-stimulating antibody conjugates (ISAC). This compound is also employed in cancer research [1].

2',3'-cGAMP sodium (2'-3'-cyclic GMP-AMP sodium) is a second messenger in cellular innate immunity, catalyzed by cGAMP synthase (cGAS) under DNA binding conditions. It binds to STING to form a dimer, inducing the production and expression of interferon-β and other cytokines.

Omaveloxolone (RTA-408) is an oral, potent, and selective activator of the nuclear factor erythropoietin-related factor 2 (Nrf2) pathway, as well as a low-potency PPARγ agonist. Omaveloxolone inhibits osteoclast formation by suppressing the STING-dependent NF-κB signaling pathway. Omaveloxolone is being investigated for use in ALS, multiple sclerosis, non-alcoholic steatohepatitis, neurodegenerative diseases, and oncology research.

MSA-2 is an orally available non-nucleotide STING agonist. The non-covalent dimer of MSA-2 binds to STING with nanomolar affinity. It shows anti-tumor activity in syngeneic mouse tumor models, synergizes with anti-PD-1, stimulates tumor secretion of interferon-β, induces tumor regression, and has long-lasting anti-tumor immunity. [3]

2',3'-cGAMP is an endogenous cyclic dinucleotide (CDN) produced by cGAS (cGAMP synthase) in response to double-stranded DNA in the cytoplasm. It acts as a STING activator and ligand, inducing interferons (IFNs) via the TBK1/IRF3 pathway and pro-inflammatory factors via the NF-κB pathway.

cAIMP acts as a STING agonist and has been shown to more effectively activate STING-dependent IRF and NF-κB signaling pathways in mammalian cells in vitro when compared to standard murine (DMXAA) and human (2',3'-cGAMP) STING agonists. In ex vivo experiments with human blood, cAIMP analogs can induce the production of type I interferons (IFNs) and pro-inflammatory cytokines.

STING-IN-12 (compound Y2) acts as an inhibitor of STING. It suppresses IFNβ gene expression induced by SR717 with an IC50 of 0.75 μM. Additionally, STING-IN-12 inhibits STING pathway activation induced by the STING agonist SR717 in THP1 cells and by MSA-2 in mice.

(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 the crucial amide benzimidazole (ABZI) component. It consistently inhibits the binding of 3 H-cGAMP to STING, with an apparent inhibition constant (IC50) of 14 μM. This compound is applicable in tumor research.

STING ligand-4 (Compound 2) is a nitro-free covalent STING inhibitor with an IC50 of less than 0.2 μM. It can be utilized in the synthesis of PROTACSTINGdegrader-4.

MSA-2-Pt is an orally active STING agonist with excellent cell membrane permeability. It can induce cell death via Pt, releasing damaged DNA to activate the cGAS-STING pathway. Additionally, MSA-2-Pt can directly activate the STING pathway through MSA-2. This compound is applicable in cancer research.

STING-IN-9 (compound 2) is a potent inhibitor of human CYP11B2. In vitro studies demonstrate that STING-IN-9 exhibits over 80-fold selectivity compared to human CYP11B1.

STING-IN-8 (Compound 15b) is a potent inhibitor of the stimulator of interferon genes (STING), with an IC50 value of 0.121 μM in humans and 0.033 μM in mice. This compound effectively inhibits STING signaling induced by MSA-2 or 2',3'-cGAMP, as well as the levels of immune and inflammatory cytokines in human and mouse cells. STING-IN-8 shows significant potential for research in STING-related inflammatory and autoimmune diseases.

The compound c-(2'FdAMP-2'FdIMP) (Compound 52) is a derivative of cAIMP and a cyclic dinucleotide (CDN). It acts as a STING agonist and significantly induces STING-dependent signaling pathways involving IRF and NF-κB. This compound is applicable in STING-based immunotherapy, including studies on cancer and infectious diseases.

STINGagonist-47 is a STING agonist with an EC50 of 0.72 μM and a Kd of 176 nM. It is a dimer of MSA-2 and is applicable in cancer research, including studies on breast cancer.

SN38-(PEG)2-Pom-α is a selective PROTACRPL15 degrader. It induces ubiquitin-mediated degradation of RPL15 without affecting TOP1. Additionally, SN38-(PEG)2-Pom-α can prompt cancer cells to secrete damage-associated molecular patterns (DAMPs), activating the cGAS-STING pathway in dendritic cells. In a human CRBN-expressing mouse melanoma model, SN38-(PEG)2-Pom-α demonstrates synergistic tumor growth inhibition when used in combination with anti-PD-1 antibodies. This compound is valuable for melanoma research.