Toll-like Receptor (TLR) Agonist

GSK2245035 is a highly potent and selective intranasal Toll-Like receptor 7 (TLR7) agonist with preferential Type-1 interferon (IFN)-stimulating properties. GSK2245035 has pEC₅₀s of 9.3 and 6.5 for IFNα and TFNα. GSK2245035 effectively suppresses allergen-induced Th2 cytokine production in human peripheral blood cell cultures. GSK2245035 is used for asthma.

Ruzotolimod (RO7020531) is an orally active TLR7 agonist. Ruzotolimod inhibits WHV viral replication and, in combination with RO-7049389 (HY-145579), inhibits AAV-HBV viral load. Ruzotolimod can be used to study infection with COVID-19 or SARS-CoV-2.

FITC-labeled ODN 1826 (sodium), a class B CpG ODN (oligodeoxynucleotide), is a TLR9 agonist. FITC-labeled ODN 1826 (sodium) can be used to evaluate CpG ODN cellular uptake and localization by confocal laser-scanning microscopy (excitation 495 nm, emission 520 nm) or flow cytometry.

L07-2 is a TLR7/8 agonist. L07-2 is a linker-toxin building block that can be used to synthesize immunostimulatory antibody conjugates (ISACs) for cancer research. L07-2 can be used to studies related to tumors such as non-small cell lung cancer.

SMU-L11 is a specific TLR7 agonist (EC₅₀=0.024 μM), which recruits MyD88 adapter protein and activates downstream NF-κB and MAPK signaling pathways. In murine models, SMU-L11 significantly enhances immune cell activation and promotes the proliferation of CD4⁺ T and CD8⁺ T cells, thereby directly killing tumor cells and inhibiting tumor growth. SMU-L11 can be used for cancer research, and also has the potential for studying immune system diseases.

SM-276001 is a potent selective TLR7 agonist that can induce antitumor immune responses. SM-276001 is an orally active interferon (IFN) inducer.

Pam2Cys (Dipalmitoyl-S-glyceryl-cysteine; S-[2,3-Bis(palmitoyloxy)propyl]cysteine) is a TLR2 agonist and immunostimulant. Pam2Cys binds to TLR2 to activate dendritic cells and trigger the TLR2-dependent NF-κB signaling pathway. Pam2Cys also induces dendritic cell maturation by upregulating the expression of cell surface MHC II molecules. Pam2Cys activates innate immune signaling pathways, drives pro-inflammatory and antimicrobial responses, enhances the expression of macrophage activation markers, increases phagocytic activity, induces the release of IL-12 and pro-inflammatory cytokines, and polarizes macrophages into a pro-inflammatory, antimicrobial phenotype without interfering with IL-10-induced macrophage polarization. Pam2Cys also serves as the lipid moiety in synthetic lipopeptide vaccines and possesses self-adjuvant properties. Pam2Cys enhances the immunogenicity of conjugated peptide segments and induces cellular and humoral immune responses. However, it does not activate CD4 T cells in mouse splenocyte cultures when used alone. Pam2Cys activates pulmonary TLR2 signaling pathways, triggers innate immune responses, recruits neutrophils and macrophages, induces the secretion of various cytokines, alleviates symptoms and damages associated with influenza A virus infection in mice without impairing adaptive immunity. Pam2Cys can be used in studies related to tuberculosis and influenza A virus infection.

Ethyl glucuronide-d₅ is the deuterium labeled Ethyl glucuronide (HY-113093). Ethyl glucuronide is an endogenous metabolite. Ethyl glucuronide is the metabolite of ethanol. Ethyl glucuronide is a biomarker for ethanol exposure that accumulates in hair and reflects the alcohol intake over a time period. Ethyl glucuronide is the agonist for TLR4.

GSK1795091 (CRX-601), an immunologic stimulator, is a synthetic TLR4 agonist. Antitumor activity. GSK1795091 can be used as a vaccine adjuvant to enhance both mucosal and systemic immunity to influenza virus vaccines. Not only, GSK1795091 inhibits tumor growth and increases the survival in mice model, but results in long term survival in influenza challenge model in mice.

CU-CPD107 is a potent, selective toll-like receptor 8 (TLR 8) agonist. CU-CPD107 inhibits TLR8 signaling. CU-CPD107 converts to synergistic agonist activities in the presence of ssRNA and induces TLR8 signaling. CU-CPD107 inhibits proinflammatory factor expression and avoids immune responses in the presence of ssRNA.

ODN 2007, a class B CpG ODN (oligodeoxynucleotide), is a Toll-like receptor (TLR) ligand. ODN 2007 can be used as an immunomodulator, vaccine adjuvant, and enhance immune responses in mammals, fish, and humans. ODN 2007 sequence: 5'-TCGTCGTTGTCGTTTTGTCGTT-3'.

TLR7 agonist 20 hydrochloride is a selective Toll-like receptor 7 (TLR7) agonist with an EC₅₀ of 0.22 μM. TLR7 agonist 20 hydrochloride, as an immunostimulant and vaccine adjuvant, enhances the production of anti-spike protein antibodies, increases IgG2b and IgG2c levels, and thereby drives Th1-type immune responses in mice. TLR7 agonist 20 hydrochloride can be used in studies related to non-inflammatory potent vaccine adjuvants.

D18 is an immune modulator. D18 acts as a TLR7/8 dual agonist (EC₅₀ = 24 nM for hTLR7 and 10 nM for hTLR8, respectively). D18 increases PD-L1 expression through epigenetic regulation, thus sensitizing tumors to PD-1/PD-L1 blockade. D18 is a ADC cytotoxin uesd for the systhesis of ADC HE-S2 (HY-144497). D18 has strong immune activation and anti-tumor activity. D18 commonly used in cancer research, such as colon cancer.

MC-Val-Cit-PAB-Amide-TLR7 agonist 4 formic (example 15) is a HER2-TLR7 and HER2-TLR8 immune agonist conjugate.

Pertuzumab zuvotolimod (SBT6050) is an anti-HER2 antibody-drug conjugate (ADC). Pertuzumab zuvotolimod is composed of a humanized anti-HER2 antibody (Pertuzumab) (HY-P9912A), a linker, a TLR8 agonist payload, and the drug-linker conjugate for ADC is Zuvotolimod (HY-145620). Pertuzumab zuvotolimod potently induces multiple anti-tumor immune activities through the direct activation myeloid cells and the subsequent induction of T and NK cell cytolytic activity. Pertuzumab zuvotolimod can be used for HER2-expressing solid tumors research.

TLR7 agonist 4 is a TLR7 agonist with pro-inflammatory cytokine-stimulating activity. TLR7 agonist 4 modulates TLR7 activity to stimulate the production of pro-inflammatory cytokines. TLR7 agonist 4 stimulates mouse bone marrow-derived macrophages to produce the pro-inflammatory cytokine TNFα. TLR7 agonist 4 can be conjugated with antibodies to form conjugates. TLR7 agonist 4 is applicable to cancer research.

RIBI-529 (RC-529) is a fully synthetic, low-toxicity TLR4 agonist vaccine adjuvant. RIBI-529 upregulates cell surface co-stimulatory molecules, receptors, cytokines and chemokines, and activates the innate immune system. RIBI-529 enhances short-term CD4⁺ T cell clonal expansion, division, and ex vivo survival under growth factor withdrawal conditions. RIBI-529 enhances humoral and cell-mediated adaptive immune responses, induces non-specific resistance against viral and bacterial pathogens, and skews responses toward a Th1 type, accompanied by Th2 responses.

MC-Val-Cit-PAB-Amide-TLR7 agonist 4 (example 15) is a HER2-TLR7 and HER2-TLR8 immune agonist conjugate.

Vidutolimod (CMP-001) is a virus-like particle containing a TLR9 activator. Vidutolimod induces human peripheral blood mononuclear cells to secrete IFNα, and upregulates the gene expression of CXCL10, PDL1, IDO and CD80. Vidutolimod activates TLR9, which in turn triggers plasmacytoid dendritic cell activation, production of IFNγ and TNFα, induction of CXCL10, and recruitment of antitumor T cells. Vidutolimod causes influenza-like symptoms, hypotension and tumor regression, and its activity depends on the presence of anti-Qβ antibodies. Vidutolimod modulates monocyte function, promotes CD4 T cell proliferation, and activates multiple immune cell types in an environment with anti-Qβ antibodies. Vidutolimod prolongs the survival of tumor-bearing mice. Vidutolimod is used in research related to advanced melanoma, head and neck squamous cell carcinoma, and advanced non-small cell lung cancer.

Pam3CSK4 is a toll-like receptor 1/2 (TLR1/2) agonist with an EC₅₀ of 0.47 ng/mL for human TLR1/2.