tlr9

TLR9-IN-1 (compound 29) is an effective and selective TLR9 inhibitor with an IC50 of 7 nM in human B cells, suitable for autoimmune diseases and inflammation.

TLR9-IN-18 is a potent and selective TLR9 antagonist. TLR9-IN-18 suppresses the production of the proinflammatory cytokine IL-6 in a CpG-induced mouse model.

Chloroquine phosphate (Aralen phosphate) is an antimalarial and anti-inflammatory agent widely used for malaria and rheumatoid arthritis. Chloroquine phosphate acts as an inhibitor of autophagy and toll-like receptors, effectively suppressing SARS-CoV-2 (COVID-19) infection (EC50 = 1.13 μM). Chloroquine phosphate can be utilized in research on autophagy, lysosomal function, and tumor diseases.

Hydroxychloroquine sulfate (Acidum iopanoicum) inhibits plasmodial heme polymerase. It is a chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa.

Hydroxychloroquine (2-[[4-[(7-Chloroquinolin-4-yl)amino]pentyl](ethyl)amino]ethanol) (HCQ) is an alkalinizing lysosomatropic drug that acts by inducing apoptosis of renal cancer cells in vitro and inhibiting TLR7/9. It is a medication used to prevent and treat malaria, and it's also being studied as an experimental treatment for COVID-19.

CU-CPT17e is a potent agonist of TLR(TLR3, TLR8, and TLR9).

E6446 inhibits Toll-like receptor (TLR)7 and 9 signaling. E6446 works in a variety of human and mouse cell types and inhibits DNA-TLR9 interaction in vitro. When administered to mice, this compound suppress responses to challenge doses of cytidine-phosphate-guanidine (CpG)-containing DNA, which stimulates TLR9.

ODN 1826 is a 20-mer DNA strand, a TLR9 agonist and an immunostimulant, with anti-tumor and cardioprotective effects, promoting apoptosis, and stimulating the production of NO and iNOS. ODN 1826 is a CpG DNA mimetic that can be used as an adjuvant for synthetic vaccines.

CpG ODN 10101 (CPG 10101) is a novel potent and selective Toll-like receptor 9 (TLR9)-containing oligodeoxynucleotide agonist with antiviral activity for the treatment of chronic infections.

Tylogenin, a steroidal aglycone generated by acid hydrolysis from two seasonal glycosides occurring in Tylophora sylvatica, inhibits IgE-induced basophil mediator release for allergic reactions. In the rabbit basophil-dependent serotonin release (BDSR) assay system, the inhibitory activity of tylogenin was significantly greater than that of its parent glycosides, tylophoroside and acetyltylophoroside, and that of dexamethasone. The activity of tylogenin was found to increase with the incubation time. In the human leukocyte-dependent histamine release test model, the glycosides had only a minimal activity. In contrast, tylogenin, with a geom mean IC50 = 49 microM, exerted a significantly greater potency than dexamethasone. These results suggest that tylogenin could represent a new class of antiallergic agents.

TLR9 antagonist1 (Compound 38) is a selective TLR9 inhibitor with an IC50 of 0.1 nM for hTLR9, demonstrating superior antagonistic activity compared to hTLR2/4/5/7/8. This compound exacerbates disease symptoms in mouse models of systemic lupus erythematosus (SLE) and raises levels of anti-dsDNA and anti-Sm antibodies. TLR9 antagonist1 is applicable in research on inflammatory and immune diseases such as lupus and arthritis.

TLR7/8/9 antagonist 2 is an orally active and highly bioavailable vTLR7/8/9 antagonist. It inhibits HEK/hTLR7, HEK/hTLR8, and HEK/hTLR9 with IC50s of 0.011 μM, 0.029 μM, and 0.052 μM, respectively. TLR7/8/9 antagonist 2 can be used to study auto-inflammatory diseases such as systemic lupus erythematosus or lupus nephritis.

ETI41 is an orally active selective TLR inhibitor that targets the nucleoside-binding site I of TLR7 (IC50= 0.63 μM) and TLR9 (IC50= 0.16 μM), without affecting surface TLRs (including TLR1/TLR2, TLR2/TLR6, TLR4, and TLR5). It demonstrates nanomolar activity in cell-based, biophysical, and in vivo studies, effectively inhibiting endosomal TLR-mediated pro-inflammatory signaling. ETI41 suppresses the expression of inflammation-related genes and significantly improves symptoms in mouse models of psoriasis and systemic lupus erythematosus (SLE). ETI41 is applicable in research related to autoimmune and inflammatory diseases.

E6446 dihydrochloride is a novel synthetic antagonist for nucleic acid-sensing TLRs; potently suppressed DNA stimulation of HEK:TLR9 cells with IC50 of 10 nM.

AT791 is an orally available TLR7 and TLR9 inhibitor, suppressing TLR7 and TLR9 signaling, used in autoimmune lupus research.

Enpatoran is an inhibitor of TLR7(IC50 = 11.1 nM) and TLR8(IC50 = 24.1 nM). Enpatoran was found to be inactive against TLR3, TLR4, and TLR9 in vitro and in vivo.

Pixatimod (also known as PG-545) is a synthetic carbohydrate-modified heparan sulfate mimetic and a Toll-like receptor 9 (TLR9) agonist. It exhibits potential immunostimulatory, antitumor, and antiviral effects. Pixatimod effectively inhibits SARS-CoV-2 by disrupting the spike protein-ACE2 interaction. Additionally, it blocks various cancer-promoting processes such as cell proliferation, invasion, metastasis, angiogenesis, and epithelial-mesenchymal transition. These effects have demonstrated significant efficacy in numerous mouse cancer models, including about 30 xenograft models and 20 syngeneic models. Pixatimod has been tested in combination with several approved anticancer compounds, showing clinical potential when used with gemcitabine, paclitaxel, sorafenib, platinum compounds, and anti-PD-1 antibodies.

Pixatimod (also known as PG-545) is a synthetic modified heparan sulfate mimetic and an agonist of Toll-like receptor 9 (TLR9), showcasing potential immunostimulatory, antitumor, and antiviral properties. It effectively inhibits SARS-CoV-2 by disrupting the interaction between the spike protein and ACE2. Moreover, Pixatimod blocks cancer-promoting processes such as cell proliferation, invasion, metastasis, angiogenesis, and epithelial-mesenchymal transition. These activities have demonstrated significant efficacy across various murine cancer models, including approximately 30 xenograft models and 20 syngeneic models. Pixatimod has been tested in combination with several approved anticancer compounds, underscoring its clinical potential, with drugs like gemcitabine, paclitaxel, sorafenib, platinum-based compounds, and an anti-PD-1 antibody.

ODN TTAGGG sodium, an inhibitory oligonucleotide (ODN), is an antagonist of TLR9, AIM2, and cGAS. It exerts immunosuppressive effects by inhibiting AIM2 inflammasome activation and cGAS activation through competitive interaction with DNA. This compound can be utilized in research on autoimmune diseases such as lupus. The sequence for ODN TTAGGG is 5'-T-T-A-G-G-G-T-T-A-G-G-G-T-T-A-G-G-G-T-T-A-G-G-G-3'.

CpG ODN 10101 sodium is a synthetic oligodeoxynucleotide (ODN) that functions as a Toll-like receptor 9 (TLR9) agonist. When combined with HH2(VQLRIRVAVIRA-NH2), it serves as an effective inducer of cytokine/chemokine expression in vitro. CpG ODN 10101 sodium stimulates dendritic cells (DC) to secrete IFN and activates B cells. It possesses antiviral and immunomodulatory properties, influencing chronic HCV infection.

ODN 1826 sodium is a class B CpG ODN (oligodeoxynucleotide) and a TLR9 agonist. It induces the production of NO and iNOS and enhances apoptosis. ODN 1826 sodium boosts immune surveillance and increases the size of atherosclerotic plaques. It exhibits antitumor activity against lung cancer, glioma, and melanoma.

ODN 2216 sodium is a human-specific TLR9 (toll-like receptor 9) ligand or agonist. It induces significant production of IFN-α and IFN-β. The compound stimulates IFN-α through pDC (plasmacytoid dendritic cells) and produces IL-12(p40) via DC (dendritic cells). ODN 2216 triggers peripheral blood mononuclear cells (PBMC) to produce IFN-γ indirectly, mediated by IFN-α/β. Additionally, ODN 2216 sodium can activate NK cells and enhance IFN-γ production in TCR-triggered CD4+ T cells.

ETI60 is an orally active selective TLR inhibitor that targets the nucleoside-binding sites I of TLR7 (IC50 = 0.68 μM) and TLR9 (IC50 = 0.12 μM) without affecting surface TLRs (including TLR1/TLR2, TLR2/TLR6, TLR4, and TLR5). It demonstrates nanomolar activity in cell-based, biophysical, and in vivo assays, effectively inhibiting endosomal TLR-mediated pro-inflammatory signaling. ETI60 modulates the expression of genes related to inflammation and significantly improves symptoms in mouse models of psoriasis and systemic lupus erythematosus (SLE). ETI60 is applicable in studies related to autoimmune and inflammatory diseases.

TLR2/9 antagonist 1 (Compound 24) is a reversible covalent antagonist of TLR2, with an IC₅₀ of 0.5 μM for TLR2/TLR6 and 0.6 μM for TLR2/TLR1, as well as TLR9, with an IC₅₀ of 0.32 μM. This compound does not significantly affect other TLR subtypes and is utilized for studying central nervous system diseases and malignancies caused by inflammation.