Toll-like Receptors

Polyinosinic-polycytidylic acid sodium is a synthetic analogue of double-stranded RNA and acts as an agonist for toll-like receptor 3 (TLR3) and RIG-I-like receptors. It serves as a potent immunomodulator, enhancing both innate and adaptive immune responses, making it valuable for vaccine development. Additionally, Poly(I:C) sodium can influence the tumor microenvironment and directly induce apoptosis in cancer cells, thus providing significant potential in cancer research and therapy.

ODN 1826 is a class B CpG oligodeoxynucleotide that acts as an agonist for Toll-like receptor 9 (TLR9). It stimulates the production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS), promoting apoptosis and enhancing immune surveillance. This compound is also associated with increased aortic atherosclerotic plaque size and exhibits antitumor activity against various cancer types, including lung cancer, glioma, and melanoma. ODN 1826 is valuable for researching immune response mechanisms and potential cancer therapies.

Afimetoran is a selective and highly bioavailable antagonist of Toll-like receptors 7 and 8 (TLR7/8). It effectively inhibits TLR7/8-mediated activation of the NF-κB signaling pathway and can reverse TLR7-induced resistance to steroid-driven apoptosis in plasmacytoid dendritic cells. This compound is particularly relevant for research into inflammation and autoimmune diseases, including systemic lupus erythematosus.

Agatolimod is a Toll-like receptor 9 (TLR9) agonist and immunomodulator with an EC50 of 180 nM. It activates TLR9 and upregulates TLR6 expression, initiating downstream signaling through IRAK4, IRF5, and IRF7. Agatolimod enhances Th1-type immune responses and promotes the activation of various immune cells, leading to increased antigen presentation, antibody regulation, cytokine secretion, apoptosis, and enhanced cytotoxicity. This compound is relevant for research into COVID-19, breast cancer, lung adenocarcinoma, HPV-related tumors, melanoma, and salmonellosis.

Robinin is a flavonoid that acts as an inhibitor of Toll-like receptors 2 and 4 (TLR2/4), modulating the TGF-β, TLR4/NF-κB, and TLR2-PI3k-AKT signaling pathways. This compound demonstrates significant anti-inflammatory and anti-tumor properties. Additionally, Robinin has been shown to enhance the anti-inflammatory effects of Methotrexate in experimental arthritis models and may mitigate cardiac toxicity induced by Doxorubicin. These attributes make Robinin a valuable reagent for research applications in inflammation and cancer therapy.

ODN M362 is a class C oligodeoxynucleotide that acts as a TLR-9 agonist, promoting immune responses through the stimulation of toll-like receptor 9. This reagent is effective in inducing apoptosis in cancer cells, making it valuable for immunological studies and the development of therapeutic vaccines. Its application as a vaccine adjuvant enhances the efficacy of antigen-specific responses in research settings.

Polyinosinic-polycytidylic acid potassium is a synthetic analog of double-stranded RNA that acts as an agonist of toll-like receptor 3 (TLR3) and retinoic acid inducible gene I (RIG-I)-like receptors. This reagent is utilized to stimulate innate and adaptive immune responses, serving as an effective vaccine adjuvant while also modifying the tumor microenvironment. Additionally, Polyinosinic-polycytidylic acid potassium can induce apoptosis in cancer cells, making it a valuable compound for cancer research and immunotherapy studies.

ODN 20844 is a TLR9 inhibitor designed to disrupt Toll-like receptor-mediated immune responses. As a guanine-modified inhibitory oligonucleotide, it specifically targets TLR7 and TLR9, leading to a reduction in immune cell activation. This compound is useful for research applications focused on modulating immune pathways and studying immune-related diseases. The sequence of ODN 20844 is 5'-TCCTGGCGc7GGGAAGT-3'.

TLR7 Agonist 3 acts as an effective agonist of Toll-like receptor 7 (TLR7), playing a significant role in the immune response modulation. This compound is utilized primarily in cancer research to explore its potential therapeutic effects in tumor immunity and the activation of anti-tumor responses. Its ability to stimulate TLR7 pathways makes it a valuable tool for investigating the mechanisms of immune activation and evaluating novel cancer treatments.

TLR7/8 Agonist 3 is a potent dual agonist of Toll-like receptors 7 and 8, designed to enhance the immune response against viral infections and tumors. This compound demonstrates significant biological activity through the activation of innate immune pathways, stimulating the production of pro-inflammatory cytokines. Research applications include immunotherapy and the study of host-pathogen interactions, making it a valuable tool for investigating TLR-mediated signaling and immune modulation.

BBIQ is an imidazoquinoline compound that acts as a potent and selective agonist for Toll-like receptor 7 (TLR7), exhibiting an EC50 of 59.1 nM in human TLR7. This compound serves as an effective vaccine adjuvant, significantly enhancing innate immune responses. BBIQ is valuable for research applications focused on immunology and vaccine development, facilitating the exploration of TLR7-mediated signaling pathways.

Imiquimod maleate is a selective toll-like receptor 7 (TLR7) agonist known for its immune response-modulating properties. It demonstrates significant antiviral and antitumor efficacy in vivo, making it a valuable compound in the study of various conditions. Research applications include the investigation of external genital and perianal warts, cancer, and COVID-19.

AZD8848 is a selective agonist of toll-like receptor 7 (TLR7) designed for research applications in asthma and allergic rhinitis. By activating TLR7, this compound enhances immune responses, making it a valuable tool for studying innate immunity and developing therapeutic strategies for related respiratory conditions.

TLR7/8 Agonist 4 is a potent agonist targeting Toll-like receptor 7 and 8. This compound enhances the activation of immune responses, exhibiting significant anti-cancer activity. Its efficacy makes it a promising tool for research in cancer immunotherapy and the study of innate immune signaling pathways.

CU-115 is a potent TLR8 antagonist with an IC50 of 1.04 µM, demonstrating selectivity for TLR8 over TLR7 (IC50 > 50 µM). This compound effectively decreases the production of pro-inflammatory cytokines, including TNF-α and IL-1β, in R-848 activated THP-1 cells. CU-115 is suitable for research applications focusing on TLR8 signaling pathways and inflammatory responses.

E104 is a potent and selective TLR7 agonist that activates immune responses through Toll-like receptor 7. This compound enhances the activity of mouse macrophages and human peripheral blood mononuclear cells (hPBMCs), making it valuable in immuno-oncology research. E104's potential for use in antibody-drug conjugate (ADC) technology further supports its application in eliciting robust anticancer effects, contributing to the development of innovative cancer therapies.

BMS905 is a potent dual inhibitor of Toll-like receptors 7 and 8, exhibiting IC50 values of 0.7 nM and 3.2 nM, respectively. This compound effectively inhibits IL-6 production induced by TLR7 or TLR8 activation in both human and mouse whole blood. BMS905 serves as a valuable tool for investigating the role of these receptors in autoimmune diseases, particularly lupus.

AXC-715 trihydrochloride is a dual agonist of Toll-like receptors 7 and 8 (TLR7/8). This compound enhances immune responses and can be utilized in the synthesis of antibody-adjuvant immunoconjugates, particularly for constructs targeting programmed death-ligand 1 (PD-L1). Its ability to stimulate TLR pathways makes AXC-715 a valuable tool for immunotherapy research and the development of therapeutic antibodies.

Bropirimine is an orally active Toll-like receptor 7 (TLR7) agonist. It has been shown to inhibit RANKL-induced osteoclast differentiation in mouse bone marrow-derived macrophages, highlighting its potential role in modulating bone metabolism. Additionally, Bropirimine exhibits dose-dependent inhibitory effects on colony formation in cultured KK-47 and 724 cells, making it a valuable tool for cancer research. This compound is relevant for studies investigating cancers and bone metabolic disorders such as osteoporosis.

PVP-037.2 is a TLR7/8 agonist that activates the immune response through the stimulation of Toll-like receptors. This compound enhances vaccine-induced TH1-type immune responses, leading to increased production of antigen-specific antibodies, particularly IgG1 and IgG2c. PVP-037.2 is valuable for research applications focused on immunology, vaccine development, and the modulation of adaptive immune responses.

SM-324405 is a potent TLR7 agonist with an EC50 of 50 nM, exhibiting pEC50 values of 7.3 for human TLR7 and 6.6 for rat TLR7. This compound is particularly useful in immunological research focused on allergic diseases. As an antedrug, SM-324405 is designed to be locally active and is rapidly metabolized to an inactive form upon systemic circulation, effectively mitigating the risk of systemic toxicity while maintaining agonistic activity in targeted environments.

3D-Monophosphoryl Lipid A-5 is a potent TLR agonist that enhances the immunogenicity of vaccines when used as an adjuvant. This compound stimulates innate immune responses, promoting the activation of various immune cells and cytokine production. It is valuable in research applications focused on vaccine development and immunotherapy, offering insights into the modulation of immune responses.

TLR8 agonist 5 is a potent agonist of Toll-like receptor 8 (TLR8), demonstrated by an EC50 of 20 nM in the HEK-Blue hTLR8 cell line. This compound effectively stimulates the immune response, making it a valuable tool for research in immunology and inflammation studies. Its ability to activate TLR8 highlights its potential applications in therapeutic development targeting immune-related pathways.

1V209 is a Toll-like receptor 7 (TLR7) agonist that exhibits anti-tumor effects through the activation of the TLR7 signaling pathway. This compound can be conjugated with various polysaccharides to enhance its water solubility, thereby improving its efficacy while maintaining low toxicity. 1V209 is suitable for research applications aimed at understanding immune responses and developing cancer immunotherapies.

ODN 24991, a guanine-modified inhibitory oligonucleotide, functions as an inhibitor of Toll-like receptors TLR3, TLR7, and TLR9. By disrupting TLR-mediated immune cell signaling, ODN 24991 serves as a valuable tool for investigating immune responses. The compound is particularly useful in research aimed at understanding the role of these TLRs in inflammation and immune regulation. ODN 24991 sequence: 5'-C-C-T-G-G-C-c7rGm-G-G-G-3'.

D18 is a dual agonist for Toll-like receptors 7 and 8 (TLR7/8), exhibiting EC50 values of 24 nM and 10 nM, respectively. This immune modulator enhances PD-L1 expression through epigenetic mechanisms, thereby increasing tumor sensitivity to PD-1/PD-L1 blockade. D18 demonstrates significant immune activation and anti-tumor effects, making it valuable in cancer research, including studies focused on colon cancer. Additionally, D18 serves as a cytotoxin for the synthesis of antibody-drug conjugate HE-S2.

AXC-715 hydrochloride is a dual agonist targeting TLR7 and TLR8. It demonstrates significant immunomodulatory activity, making it a valuable tool in the development of antibody-adjuvant immunoconjugates. This compound can be utilized to enhance the efficacy of therapies targeting programmed death-ligand 1 (PD-L1) by linking it to one or more adjuvants, advancing research in cancer immunotherapy and immune response modulation.

TLR4/NF-κB-IN-1 is a selective inhibitor of the TLR4/NF-κB signaling pathway, demonstrating significant anti-inflammatory properties. This compound exhibits the ability to penetrate the blood-brain barrier, making it suitable for studies involving neuroinflammation. In murine models, TLR4/NF-κB-IN-1 effectively reduces acute neuroinflammation induced by lipopolysaccharides (LPS) while downregulating the expression of TLR4, phosphorylated NF-κB, and phosphorylated IκB-α proteins, providing a valuable tool for researching neuroinflammatory processes and their therapeutic modulation.

TLR8 antagonist-1 is a selective antagonist targeting Toll-like receptor 8 (TLR8). It effectively inhibits TLR8-mediated inflammatory responses and associated signaling pathways, including the recruitment of MyD88 and the activation of NF-κB and IRF pathways. This compound demonstrates significant anti-inflammatory activity, making it a valuable tool for research in inflammation and immune response modulation.

BNT411 is a selective TLR7 agonist known for its ability to stimulate the production of interferon-alpha (IFNa) both in vivo and in vitro. This compound exhibits anticancer properties, making it a valuable tool in cancer research, particularly for non-small cell lung cancer, pancreatic cancer, and untreated extensive-stage small cell lung cancer (ES-SCLC). Its mechanism of action and efficacy in activating immune responses make it a key reagent for investigating cancer immunotherapy.

TLR7/8 antagonist 2 is a potent antagonist specifically targeting Toll-like receptors 7 and 8, with IC50 values of 4.9 nM and 0.6 nM, respectively. This compound is essential for studying the role of TLR7 and TLR8 in autoimmune diseases, such as systemic lupus erythematosus, where their inappropriate activation contributes to pathogenesis. TLR7/8 antagonist 2 holds significant potential for advancing research in the field of autoimmune disorders.

TLR7/8 Agonist 6 is a potent agonist of Toll-like receptors 7 and 8, exhibiting IC50 values of 0.18 μM and 5.34 μM, respectively. As an imidazoquinoline derivative, this compound plays a crucial role in enhancing immune responses. It is particularly valuable in the investigation of immunomodulatory therapies for infectious diseases, cancer, and autoimmune disorders.

ODN D-SL01 is a class B CpG oligodeoxynucleotide that acts as a TLR9 agonist. It exhibits potent immunostimulatory properties in various vertebrate species and demonstrates anticancer activity. The specific sequence of ODN D-SL01 is 5'- T-C-G-C-G-A-C-G-T-T-C-G-C-C-C-G-A-C-G-T-T-C-G-G-T-A-3'. This compound is valuable for research applications focused on immune modulation and cancer therapy.

SM-276001 is a potent selective TLR7 agonist known for its ability to induce antitumor immune responses. This compound acts as an orally active interferon inducer, enhancing the body’s immune system to target and combat tumor cells. It is particularly useful in cancer research and immunotherapy studies aimed at understanding TLR7-mediated pathways in the immune response.

M62812 is a selective toll-like receptor 4 (TLR4) inhibitor that attenuates endothelial and leukocyte activation. By inhibiting TLR4 signaling, M62812 effectively diminishes LPS-induced coagulation and inflammatory responses, offering protective effects against lethal septic shock in murine models. This reagent serves as a valuable tool for research focused on the mechanisms of sepsis and related inflammatory disorders.

GSK1795091 is a synthetic TLR4 agonist that serves as a potent immunologic stimulator. It demonstrates significant antitumor activity by inhibiting tumor growth and enhancing survival in murine models. Additionally, GSK1795091 acts as an effective vaccine adjuvant, improving both mucosal and systemic immune responses to influenza virus vaccines, and has been shown to promote long-term survival in influenza challenge models. This compound is valuable for research applications in immunology and cancer therapeutics.

Ruzotolimod is an orally active TLR7 agonist that demonstrates potent antiviral effects by inhibiting viral replication of the Woodchuck hepatitis virus (WHV). Additionally, in combination with RO-7049389, it effectively reduces AAV-HBV viral load. This compound is valuable for research applications involving viral infections, including studies on COVID-19 or SARS-CoV-2.

TLR7/8/9 Antagonist 2 is a potent orally active inhibitor targeting Toll-like receptors 7, 8, and 9. It demonstrates significant inhibitory effects on HEK/hTLR7, HEK/hTLR8, and HEK/hTLR9, with IC50 values of 0.011 μM, 0.029 μM, and 0.052 μM, respectively. This compound exhibits high bioavailability in vivo, making it a valuable tool for investigating auto-inflammatory diseases, including systemic lupus erythematosus and lupus nephritis.

CU-CPD107 is a selective toll-like receptor 8 (TLR 8) agonist that modulates TLR 8 signaling pathways. This compound enhances immune responses when co-administered with single-stranded RNA (ssRNA), leading to synergistic activation of TLR 8. Additionally, CU-CPD107 suppresses the expression of pro-inflammatory factors, mitigating unwanted immune responses in the presence of ssRNA. This reagent is valuable for research into TLR 8's role in immune modulation and inflammation.

T5342126 is a potent antagonist of Toll-like receptor 4 (TLR4), designed to modulate immune responses. It effectively inhibits lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 cells, with an IC50 of 27.8 μM. Additionally, T5342126 reduces LPS-induced production of pro-inflammatory cytokines, including IL-8, TNF-α, and IL-6 in isolated human whole blood, with IC50 values of 110.5 μM, 315.6 μM, and 318.4 μM, respectively. In vivo, T5342126 (82 mg/kg) decreases ethanol consumption and mitigates microglial activation, as indicated by reduced Iba1 levels, in the central nucleus of the amygdala of ethanol-dependent mice, highlighting its potential in neurological research.

ODN 2336 is a potent TLR9 agonist classified as an A-Class CpG oligodeoxynucleotide (ODN). It effectively stimulates the production of interferon-alpha (IFN-α) and upregulates the expression of IP-10 and IL-18 mRNA. ODN 2336 serves as a valuable adjuvant in vaccine development and research, enhancing immune responses and providing insights into nucleic acid-based immunotherapy.

Pam2Cys is a TLR2 agonist that acts as an immunostimulant by binding to TLR2, activating dendritic cells, and initiating the TLR2-dependent NF-κB signaling pathway. This compound promotes dendritic cell maturation through the upregulation of MHC II molecules, enhances innate immune signaling, and drives pro-inflammatory responses, including the release of IL-12 and other cytokines. Additionally, Pam2Cys serves as a lipid moiety in synthetic lipopeptide vaccines, boosting immunogenicity, while selectively inducing pro-inflammatory macrophage activation. Research applications include studies on tuberculosis and influenza A virus infections, as it effectively recruits immune cells and mitigates infection-related symptoms without compromising adaptive immunity.

INI-4001 is a TLR7/8 agonist that modulates innate and adaptive immune responses by activating both murine TLR7 and human TLR7/TLR8 pathways. This compound enhances immunological responses, leading to increased IgG and neutralizing antibodies against Powassan virus (POWV) while concurrently reducing viral loads in multiple organs, including the brain and liver. INI-4001 also provides complete protection from lethal POWV challenges and promotes a Th1-biased immune response. It has demonstrated efficacy when used in combination with aluminum hydroxide and SARS-CoV-2 RBD antigen, making it valuable for research on Powassan virus infection and COVID-19 immunology.

TLR7 Agonist 4 is a potent TLR7 agonist, exhibiting an EC50 of 4.3 nM. This compound activates TLR7, a key receptor in the innate immune response, facilitating the advancement of research in immunology and inflammatory diseases. Its specific biological activity makes it suitable for studies involving viral infections, autoimmunity, and cancer therapy applications.

SjDX5-271 is a small peptide inhibitor targeting the TLR4/MyD88/NF-κB signaling pathway. It is known to induce cell polarization and mitigate hepatic inflammation, demonstrating protective effects against liver ischemia-reperfusion injury in mouse models. This compound is valuable for research in immunology and liver-related inflammation studies.

Eritoran tetrasodium is a Toll-like receptor 4 (TLR4) antagonist with notable anti-inflammatory properties. It has demonstrated the ability to protect against lethal infections caused by viruses such as influenza, Ebola virus (EBOV), and Marburg virus (MARV). By decreasing granulocytosis, Eritoran tetrasodium may also alleviate the severity associated with cytokine storms. The compound plays a significant role in inhibiting the pathogenesis of filovirus infections, making it valuable for research applications in virology and immunology.

ODN 21158 is a selective inhibitor of Toll-like receptors 3 (TLR3) and 9 (TLR9). It effectively reduces interferon-alpha (IFN-α) secretion in a dose-dependent manner without exhibiting cytotoxic effects. This reagent is valuable for research applications involving immune modulation and the study of innate immune responses.

a15:0-i15:0 PE is a diacyl phosphatidylethanolamine that functions as a non-canonical agonist for the TLR2-TLR1 heterodimer. It exhibits significant immunogenic activity, activating both T cells and dendritic cell signaling pathways while also demonstrating anti-inflammatory properties. a15:0-i15:0 PE promotes the production of pro-inflammatory cytokines such as TNFα and IL-6 and constitutes approximately 50% of the lipid membrane in A. muciniphila, highlighting its biological relevance in microbiome studies and immune response research.

Vidutolimod (CMP-001) is a CpG-A oligodeoxynucleotide that acts as a Toll-like receptor 9 (TLR9) agonist. It effectively activates plasmacytoid dendritic cells (pDCs), resulting in the release of interferon alpha (IFNα). This mechanism initiates a series of anti-tumor immune responses, making Vidutolimod a valuable tool for cancer immunotherapy research and the study of immune modulation.

SMU-CX1 is a selective TLR3 inhibitor with an IC50 of 0.11 μM, demonstrating effective inhibition across various influenza A virus subtypes, with IC50 values ranging from 0.14 to 0.33 μM. Additionally, SMU-CX1 shows antiviral activity against SARS-CoV-2, targeting viral PB2 and NP proteins with an IC50 of 0.43 μM. Furthermore, SMU-CX1 modulates the inflammatory response in host cells by inhibiting key factors such as IFN-β, IP-10, and CCL-5, making it a valuable tool for research in virology and innate immune response.