Toll-like Receptor (TLR) Inhibitor

Raffinose (Melitose) regulates intestinal flora, inhibits TLR4-MyD88-NF-κB signaling pathway, and activates Nrf2 signaling pathway. Raffinose exhibits anti-inflammatory, antioxidant, and immunomodulatory activities. Raffinose is orally active.

Atibuclimab (IC14), is a chimeric monoclonal antibody directed against CD14 and is composed of murine variable and human IgG4 Fc regions. Atibuclimab attenuates Lipopolysaccharides (HY-D1056) (LPS)-induced symptoms and strongly inhibits LPS-induced proinflammatory cytokine release, while only delaying the release of the anti-inflammatory cytokines soluble TNF receptor type I and IL-1 receptor antagonist. Atibuclimab can be used for the research of amyotrophic lateral sclerosis, sepsis, community-acquired pneumonia, or acute lung injury.

Tomaralimab (OPN-305) is a humanized anti-TLR2 IgG4 monoclonal antibody. Tomaralimab inhibits TLR2, MyD88, NLRP3, and reduces pro-inflammatory cytokine (IL-1β, IL-6, IL-8) production. Tomaralimab reduces tau pathology. Tomaralimab improves cognition, atopic dermatitis. Tomaralimab has anticancer effects on pancreatic ductal adenocarcinoma. Tomaralimab is being studied in myelodysplastic syndrome (MDS), atopic dermatitis, pancreatic ductal adenocarcinoma, Alzheimer's disease, and myocardial ischemia/reperfusion injury.

IRF5-CPP5 is a cytosolic peptide that selectively targeting human IRF5 wirh a K_d of 0.53 μM. IRF5-CPP5 disrupts IRF5 homodimerization and inhibits its nuclear translocation without altering IRF5 phosphorylation levels. IRF5-CPP5 inhibits proinflammatory cytokine (IL-6, IL-1β, TNF-α) production. IRF5-CPP5 can be used for the research of systemic lupus erythematosus.

Chloroquine (phosphate) (Standard) is the analytical standard of Chloroquine (phosphate). This product is intended for research and analytical applications. Chloroquine phosphate is an antimalarial and anti-inflammatory agent widely used to treat malaria and rheumatoid arthritis. Chloroquine phosphate is an autophagy and toll-like receptors (TLRs) inhibitor. Chloroquine phosphate is highly effective in the control of SARS-CoV-2 (COVID-19) infection in vitro (EC₅₀=1.13 μM).

CL264 is a TLR7-specific agonist for innate immune signals research.

KM91104 is a cell-permeable V-ATPase a3-b2 inhibitor (IC₅₀ = 2.3 µM). KM91104 reduces the metabolic activity, cell proliferation capacity and V-ATPase subunit protein expression levels of primary human hepatic stellate cells, increases intracellular ATP levels and decreases cytoplasmic pH. KM91104 reduces TLR4 expression on the surface of oligodendrocyte precursor cells, blocks the ENV-TLR4 interaction, and reverses oligodendrocyte myelination defects induced by ENV protein.

(±)-Naringenin is an orally available anti-inflammatory agent that can regulate both acute and chronic inflammation responses, while also showing antioxidant, neuroprotective, liver-protective, and anti-cancer effects. (±)-Naringenin promotes vasodilation in endothelial cells by activating BK_Ca channels in muscle cells. It also exerts protective effects against experimental colitis by inhibiting Toll-like receptor 4/NF-κB signaling, making it useful in studies related to sepsis, fulminant hepatitis, fibrosis, and cancer research.

Atazanavir (BMS-232632) sulfate is a highly selective and orally active HIV-1 protease inhibitor with blood-brain barrier permeability. Atazanavir sulfate is a substrate and inhibitor of CYP3A4, and an inhibitor of P-glycoprotein (P-gp). Atazanavir sulfate is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 3.49 μM. Atazanavir sulfate inhibits cardiac fibrosis, hyperlipidemia and induces malignant glioma death.

TLR4-IN-C34-C2-COO is a linker that incorporates TLR4 inhibitor TLR4-IN-C34. TLR4-IN-C34-C2-COOH can be used in the research of inflammation and acute myocardial injury. TLR4-IN-C34 inhibits TLR4 in enterocytes and macrophages, and reduces systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis.

AN-3485 is a benzoxaborole analogue and an orally active antagonist of the Toll-like pathway. AN-3485 can inhibit TLR-mediated inflammatory cytokine secretion and has significant anti-inflammatory activity. In addition, AN-3485 also has certain anti-tumor activity.

Xelafaslatide (ONL-1204) is a Fas receptor antagonist. Xelafaslatide blocks the Fas receptor signaling pathway and inhibits downstream apoptosis and inflammatory pathways. Xelafaslatide suppresses neuroinflammation and microglial activation in glaucoma models, protects retinal ganglion cells and prevents axonal degeneration. Xelafaslatide is applicable to relevant research on glaucoma.

Gypenoside XLIX is a multifunctional bioactive compound that can be isolated from Gynostemma pentaphyllum, with a K_a value of 1.58 μM for its binding to SIRT1. Gypenoside XLIX acts as a PPAR-α agonist. It inhibits the activation of TLR4-mediated NF-κB signaling pathway by activating the Sirt1/Nrf2 signaling pathway, reduces ROS accumulation, and alleviates hepatic inflammatory injury in mice with sepsis-induced liver disease. Gypenoside XLIX targets SIRT1 to block YAP-NLRP3 activation and improve sepsis-induced cardiomyopathy. Gypenoside XLIX inhibits apoptosis (Apoptosis), pyroptosis (Pyroptosis), autophagy (Autophagy), lipid peroxidation, pro-inflammatory cytokines and anti-inflammatory cytokines. Gypenoside XLIX alleviates sepsis-induced splenic injury by inhibiting inflammation and oxidative stress, and mitigates sepsis-associated encephalopathy by targeting PPAR-α. Gypenoside XLIX prevents acute kidney injury by inhibiting IGFBP7/IGF1R-mediated programmed cell death and inflammation. Gypenoside XLIX inhibits the expression and activity of vascular cell adhesion molecule-1 in cytokine-induced human endothelial cells. Gypenoside XLIX is applicable to research related to acute liver injury, lung injury, cardiomyopathy, acute splenic injury, sepsis-associated encephalopathy, acute kidney injury, atherosclerosis and chronic inflammation.

Procyanidin B3 is a natural product with antioxidant activity and oral bioavailability, possessing good blood-brain barrier penetration. Procyanidin B3 is a selective inhibitor of histone acetyltransferase (HAT). By inhibiting p300 HAT-mediated acetylation of the androgen receptor (androgen receptor). Procyanidin B3 alleviates intervertebral disc degeneration (IVDD) by inhibiting the formation of the TLR4/MD-2 complex. Procyanidin B3 can be used in research on prostate cancer and arthritis.

Pamidronate disodium (CGP 23339A), the second-generation nitrogen-containing bisphosphonate, is an inhibitor of bone loss. Pamidronate disodium significantly inhibits subchondral bone loss in early osteoarthritis by upregulating the expression of osteoprotegerin in cartilage and subchondral bone, and inhibiting the expression of RANKL and MMP-9 in both tissues, as well as TLR-4 in cartilage, thereby alleviating cartilage degeneration. Additionally, Pamidronate disodium can inhibit the signaling of Wnt and β-catenin, and is applicable for research on osteoporosis and osteosarcoma.

D-Allose exhibits antitumor activity against various cancer cells. D-Allose scavenges reactive oxygen species (ROS) and reduces oxidative stress damage. D-Allose exhibits anti-inflammatory and neuroprotective through inhibition of TLR4/PI3K/AKT signaling pathway. D-Allose exhibits antihypertensive, cryoprotective, and anti-osteoporotic activities.

Inotodiol activates p53 signaling pathway, inhibits MMP-2/9, and exhibits antitumor activity in cancer cell HeLa. Inotodiol inhibits the generation of ROS and exhibits antioxidant and neuroprotective effects. Inotodiol inhibits the activation of MAPK and NF-κB signaling pathway, and exhibits anti-inflammatory activity. Inotodiol inhibits TLR-4 mediated TNF-α production (IC₅₀s in BMMC and BMDM is 0.7 μM and 3.0 μM), inhibits the degranulation in mast cell, exhibits anti-allergic activity. Inotodiol is orally active.

Phellopterin, an orally active furocoumarin with multiple biological activities. Phellopterin is a partial agonist of the central benzodiazepine receptors. Phellopterin exerts anti-inflammatory effects by upregulating SIRT1, downregulating ICAM-1 (reducing chronic inflammation, aiding diabetic ulcer healing), inhibiting STAT3 phosphorylation (easing atopic dermatitis inflammation), regulating Akt/PKC pathways (lowering TNF-α-induced VCAM-1 to block monocyte adhesion), and inhibiting TLR4/NF-κB pathway and macrophage M2 polarization (alleviating colitis-related cancers). Phellopterin suppresses ovarian cancer progression via inhibiting the PU.1/CLEC5A/PI3K-AKT loop (inducing cell cycle arrest, apoptosis, DNA damage). Phellopterin alleviates murine diabetes by promoting adipocyte differentiation and increasing PPARγ. Phellopterin also has anti-HSV-1 activity. Phellopterin can be used for studying anti-inflammation, anti-cancer (e.g., ovarian cancer, colitis cancer), blood glucose lowering, anti-diabetes, and anti-virus.

MD2-IN-1 is an inhibitor of Myeloid differentiation protein 2 (MD2) with a KD of 189 μM for the recombinant human MD2 (rhMD2).

MD2-TLR4-IN-1 is a myeloid differentiation protein 2/toll-like receptor 4 (MD2-TLR4) complex antagonist. MD2-TLR4-IN-1 inhibits Lipopolysaccharides (HY-D1056) (LPS)-induced expression of TNF-α and IL-6 in macrophages with IC₅₀ values of 0.89 μM and 0.53 μM, respectively. MD2-TLR4-IN-1 can be used for the study of acute lung injury (ALI).