TLR4
TLR4 is a pattern-recognition receptor that detects bacterial lipopolysaccharide (LPS) and drives innate immune activation with pro-inflammatory cytokine and chemokine production[1]. Mechanistically, TLR4-MD-2 recognizes LPS, and the solved TLR4-MD-2-LPS structure explains ligand recognition and receptor activation[2]. After LPS engagement, TLR4 signals through TIRAP-MyD88 at the plasma membrane and then through TRAM-TRIF from early endosomes to induce interferon-β responses[3]. Therefore, TLR4 trafficking links receptor localization to inflammatory signaling magnitude and duration[4]. In disease models, abnormal TLR4 signaling associates with sepsis, endotoxemia, acute lung injury, rheumatoid arthritis, and cardiovascular diseases[5]. Compared with related TLR isoforms, TLR4 is distinguished by LPS recognition through the MD-2 complex and sequential MyD88/TRIF signaling[2][3]. For experimental applications, TLR4 inhibitors may downregulate TLR4, bind TLR4 or TLR4/MD-2, or bind MD-2 to suppress pathway activation[5]. However, eritoran, an MD2-TLR4 antagonist, did not significantly reduce sepsis-induced mortality in a phase 3 trial[6].
References:
- [1]. Vaure C, et al. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol. 2014 Jul 10;5:316. [Content Brief]
- [2]. Park BS, et al. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature. 2009 Apr 30;458(7242):1191-5. [Content Brief]
- [3]. Kagan JC, et al. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat Immunol. 2008 Apr;9(4):361-8. [Content Brief]
- [4]. Ciesielska A, et al. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell Mol Life Sci. 2021 Feb;78(4):1233-1261. [Content Brief]
- [5]. Zhang Y, et al. Toll-like receptor 4 (TLR4) inhibitors: Current research and prospective. Eur J Med Chem. 2022 May 5;235:114291. [Content Brief]
- [6]. Opal SM, et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA. 2013 Mar 20;309(11):1154-62. [Content Brief]
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TLR4 Inhibitors
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TLR4 Agonists
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TLR4 Antagonists
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TLR4 Chemical
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TLR4/CD284 Proteins
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TLR4 Related Products (103)
Related Products (103)
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Recombinant Proteins (1)
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IAXO-101 iodide
0 ImagesCat. No.: HY-129684CAS No.: 1202388-64-4IAXO-101 iodide is a TLR4/CD14 blocker. IAXO-101 iodide can inhibit the innate immune pathway of CD14. IAXO-101 iodide is capable of improving the recording performance of intracortical microelectrodes in mice. IAXO-101 iodide can also partially alleviate fetal growth restriction, placental vascular damage, and reduce the level of the inflammatory factor TNF-α in pregnant mice infected with malaria. IAXO-101 iodide can be used in the research of gestational malaria and inflammatory diseases.
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Antimicrobial Peptide YD
0 ImagesCat. No.: HY-P11913CAS No.: 2124174-65-6Antimicrobial Peptide YD is an Antimicrobial peptide. Antimicrobial Peptide YD attenuates the TLR4/MYD88/NF-κB signaling pathway, inhibits ROS production, upregulates the expression of antioxidant enzymes, reduces the levels of inflammation-related factors, and prevents the downregulation of E-cadherin and upregulation of Vimentin. Antimicrobial Peptide YD exhibits activity against Gram-positive bacteria, Gram-negative bacteria, and multidrug-resistant bacteria. Antimicrobial Peptide YD possesses anti-inflammatory, antifibrotic, and antioxidant effects. Antimicrobial Peptide YD can be used in pulmonary fibrosis research.
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Tri(TLR4-IN-C34-C2-amide-PEG1)-amide-C3-COOH
0 ImagesCat. No.: HY-145253Tri(TLR4-IN-C34-C2-amide-PEG1)-amide-C3-COOH is a linker that incorporates TLR4 inhibitor TLR4-IN-C34. TLR4-IN-C34 inhibits TLR4 in enterocytes and macrophages, and reduces systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis.
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D-Glucuronic acid sodium salt monohydrate
0 ImagesD-Glucuronic acid sodium salt monohydrate is a major component of many anti-inflammatory proteoglycans, which can promote embryonic development and inhibit cell aggregation. After being metabolized into ethyl glucuronide (HY-113093), D-Glucuronic acid sodium salt monohydrate activates Toll-like receptor 4 (TLR4), causing pain. D-Glucuronic acid sodium salt monohydrate and its derivative glucurono-lactone can serve as liver detoxifiers, and its derivatives also possess anti-tumor activity.
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Xanthine oxidase-IN-6
0 ImagesCat. No.: HY-146560Xanthine oxidase-IN-6 (Compound 6c) is a potent, orally active, mixed-type xanthine oxidase (XOD) inhibitor with an IC50 value of 1.37 µM. Xanthine oxidase-IN-6 shows strong anti-hyperuricemia and renal protective activity.
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Dendrocandin U
0 ImagesCat. No.: HY-N21802CAS No.: 1922084-93-2Dendrocandin U is a bibenzyl compound found in Dendrobium officinale that exhibits anti-inflammatory activity and α-glucosidase inhibitory effect (IC50 = 9.46 mM). Dendrocandin U inhibits the expression of TLR4 and MyD88 in the TLR4/MyD88/NF-kB pathway, suppresses the phosphorylation of NF-kB p65 and I-kBα, and blocks the nuclear translocation of NF-kB p65. Dendrocandin U inhibits M1 polarization, NO secretion, and TNF-α release in alveolar macrophages, and reduces inflammatory morphological changes in macrophages. Dendrocandin U promotes neurite outgrowth in PC12 cells. Dendrocandin U can be used for research on inflammation-related diseases and type 2 diabetes.
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LM9
0 ImagesCat. No.: HY-180336CAS No.: 2249864-11-5LM9 is a potent, orally active MyD88 inhibitor. LM9 blocks TLR4/MyD88 binding, MyD88 homodimer formation, and TLR4/MyD88/NF-κB signaling pathway activation. LM9 prevents atherosclerosis by regulating inflammatory responses and oxidative stress in macrophages. LM9 efficiently mitigates inflammatory responses and fibrosis in obesity-induced cardiomyopathy. LM9 can be used for fibrosis and atherosclerosis research.
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PTPRO-IN-1
0 ImagesCat. No.: HY-183573PTPRO-IN-1 is a selective, orally active PTPRO inhibitor with an IC50 of 0.16 μM. PTPRO-IN-1 exhibits IC50 values of 2.4 μM, 2.33 μM and 2.13 μM against PTPN22, PTP1B and PTPRT, respectively, and shows almost no inhibitory activity against STEP/SSH2. PTPRO-IN-1 inhibits the TLR4/NF-κB signaling pathway in macrophages, ameliorates colonic pathological conditions and suppresses the secretion of pro-inflammatory cytokines by T cells. PTPRO-IN-1 can be used for the research of inflammatory bowel disease.
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β-Funaltrexamine
0 ImagesCat. No.: HY-160938CAS No.: 72782-05-9Synonyms: β-FNAβ-Funaltrexamine (β-FNA) is a blood-brain barrier-permeable, selective and irreversible μ-opioid receptor antagonist with immunomodulatory, anti-inflammatory and neuroprotective activities. β-Funaltrexamine inhibits p38 MAPK and TLR4 signaling by blocking μ-opioid receptors, and reduces the transcriptional activities of NF-κB, AP-1, CREB and Stat. Furthermore, β-Funaltrexamine inhibits iNOS activation and pro-inflammatory microglial polarization, converting microglia to an anti-inflammatory phenotype, thereby downregulating neuroinflammation and ameliorating neuronal degeneration. β-Funaltrexamine is widely applicable to research related to stroke, cerebral ischemia/reperfusion injury and neurodegenerative diseases.
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rel-TLR4-IN-2
0 ImagesCat. No.: HY-173388ACAS No.: 1010705-14-2rel-TLR4-IN-2 (Compound 13) is a biologically active indane compound with anti-inflammatory activity. rel-TLR4-IN-2 exerts anti-inflammatory effects by inhibiting the TLR4 signaling pathway. rel-TLR4-IN-2 can be used for the research of inflammatory diseases.
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Rabeximod
0 ImagesCat. No.: HY-14750CAS No.: 872178-65-9Synonyms: ROB-803Rabeximod (ROB-803), an anti-rheumatic compound, impairs the differentiation and function of human pro-inflammatory dendritic cells and macrophages via downregulating TLR2 and TLR4 stimulation. Rabeximod (ROB-803) is used for rheumatoid arthritis (RA) research.
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GAP214
0 ImagesCat. No.: HY-182034GAP214 is a monosaccharide lipid A analogue and TLR4/MD-2 complex modulator.GAP214 binds to the TLR4/MD-2 complex via hydrophobic interactions, salt bridges, and hydrogen bonds, induces dimerization of the complex to initiate intracellular signaling cascades.GAP214 functions as an immunostimulant and vaccine adjuvant, enhances antigen-specific IgG antibody production in a mouse model.
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CCL-34
0 ImagesCat. No.: HY-176755CAS No.: 943316-60-7CCL-34 is a Toll-like receptor 4 (TLR4) activator. CCL-34 significantly induced dendritic cell (DC) CD83 expression and IL-12p70 production in a dose-dependent manner, thereby inducing DC maturation. CCL-34 enhanced the allostimulatory activity of DC on naive CD4+CD45+RA+ T cell proliferation and IFN-γ secretion. CCL-34 further induced antigen presentation ability in mice inoculated with doxorubicin-treated colorectal cancer cells. CCL-34 can be used in studies of immune stimulation.
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Lytx-Pa2a
0 ImagesCat. No.: HY-P11442Synonyms: Lycotoxin-Pa2a; TBIU041425Lytx-Pa2a (Lycotoxin-Pa2a) is a peptide inhibitor against bacterial membranes and TLR4 receptor. Lytx-Pa2a exerts antimicrobial effects via non-competitive disruption of outer/cytoplasmic membranes and suppression of LPS-induced TLR4/NF-κB signaling. Lytx-Pa2a is promising for research of bacterial infection and inflammation-related disease (e.g., sepsis).
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HCN-IN-1
0 ImagesCat. No.: HY-186062CAS No.: 2234283-04-4HCN-IN-1 is a TLR4 inhibitor and HCN channel modulator with activity against HCN2 and HCN4.HCN-IN-1 inhibits TLR4-mediated alkaline phosphatase (SEAP) signal activity.HCN-IN-1 reduces HCN2 current across tested voltages, shifts voltage-dependent activation to more hyperpolarized potentials, slows activation kinetics, and does not affect deactivation process.HCN-IN-1 blocks HCN4 current.HCN-IN-1 exhibits analgesic, anti-inflammatory, and anti-anginal effects.HCN-IN-1 can be used for the research of inflammatory pain, neuropathic pain, heart failure, inflammation.
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Papiliocin
0 ImagesCat. No.: HY-P11093Papiliocin is a potent peptide antibiotic with both anti-inflammatory and antibacterial activities. Papiliocin is primarily active against Gram-negative bacteria. Papiliocin exhibits strong anti-inflammatory activity against cell, exerting its anti-inflammatory activity by inhibiting the production of NO and the secretion of TNF-α and MIP-2. Papiliocin participates in the innate defense response mechanism by inhibiting the Toll-like receptor pathway and NF-κB. Papiliocin induces apoptosis in fungal cells and increases the total level of intracellular ROS. Papiliocin acts as an effective antiseptic peptide in sepsis models. Papiliocin is useful in anti-inflammatory and antibacterial research.
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Liriodendrin
0 ImagesLiriodendrin is an orally effective lignan compound with anti-inflammatory, antioxidant, and anti-platelet aggregation activities. Liriodendrin is isolated and extracted from Sargentodoxae caulis and Linaria vulgaris. Liriodendrin regulates the expression of genes related to inflammation and cellular metabolism by inhibiting the NF-κB, PI3K/Akt, and TLR4 signaling pathways, or by activating the PI3K-DDX18 pathway. Liriodendrin increases the expression of HSF1 and HSP27 without cytotoxicity. Liriodendrin is used in studies on ulcerative colitis, myocardial ischemia-reperfusion injury, sepsis-induced acute lung injury, and chronic endometritis.
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Lard oil
0 ImagesCat. No.: HY-W127601CAS No.: 8016-28-2Lard oil is an orally active biochemical reagent. Lard oil upregulates PERK, eIF2a, CHOP, OPN, TLR2, TLR4, TNF-α, and downregulates GRP78 and IRE1a. Lard oil induces responses such as body fat accumulation, elevated serum insulin levels, increased HOMA-IR, hepatic ectopic lipid deposition, hepatic endoplasmic reticulum stress, and hepatic inflammation. Lard oil can be used in studies related to diet-induced obesity, insulin resistance, and non-alcoholic fatty liver disease.
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N-(p-Coumaroyl) Serotonin (Standard)
0 ImagesCat. No.: HY-129440RCAS No.: 68573-24-0N-(p-Coumaroyl) Serotonin (Standard) is the analytical standard of N-(p-Coumaroyl) Serotonin (HY-129440). This product is intended for research and analytical applications. N-(p-Coumaroyl) Serotonin is an orally active polyphenol found in safflower seeds with potent anti-inflammatory, antioxidant, and antitumor activities. N-(p-Coumaroyl) Serotonin suppresses NF‑κB, TLR4/MyD88 and MAPK signaling, activates NQO1/HO‑1 pathways, and inhibits pro‑inflammatory cytokines, iNOS and COX‑2 and ROS production. N-(p-Coumaroyl) Serotonin induces S‑phase arrest and apoptosis in glioblastoma cells, reduces atherosclerotic lesions, and alleviates renal and vascular injuries. N-(p-Coumaroyl) Serotonin acts as a vasodilator, regulates calcium dynamics. N-(p-Coumaroyl) Serotonin can be used for the research of neurodegenerative diseases, atherosclerosis, glioblastoma, and acute renal failure.
