tlr 4

TLR4-IN-C34 is an inhibitor of TLR4, and reduces systemic inflammation in models of endotoxemia and necrotizing enterocolitis

IAXO-102 is a TLR4 antagonist that negatively regulates TLR4 signaling by inhibiting MAPK and p65 NF-κB phosphorylation, as well as the expression of TLR4-dependent proinflammatory proteins. It also prevents the development of experimental abdominal aortic aneurysm.

Resatorvid (TAK-242), a selective Toll-like receptor 4 (TLR4) inhibitor, binds directly to Cys747 to prevent TLR4-TIRAP interaction, thereby blocking downstream signaling. Resatorvid exhibits antitumor, anti-inflammatory, and neuroprotective activities.

Rabeximod is a potent immunomodulator that reduces the severity of autoimmune diseases in rat models. Rabeximod inhibits arthritis in a time-dependent manner by stimulating TLR2 and TLR4 downstream to block the activation of inflammatory cells, most likely macrophages. Rabeximod effectively reduces brain antigen presentation in mice during anti-inflammatory therapy for traumatic brain injury.

ABR-238901 is an oral, active S100A8/A9 blocker that inhibits the interaction of S100A8/A9 with its receptors RAGE(receptor for advanced glycation end products) and TLR4 (toll-like receptor 4). ABR-238901 has potential as a compound for the treatment of myocardial infarction (MI).

Chloranil (tetrachloro-p-benzoquinone) triggers inflammation and neurological dysfunction through Toll-like receptor 4 signaling and can be used to model inflammation in mice.

RV01 is a novel quinoline-substituted analogue of resveratrol that inhibits DNA damage, reduces ethanol-induced acetaldehyde dehydrogenase (ALDH2) mRNA expression, and has hydroxyl radical scavenging activity. rV01 reduces iNOS expression and has anti-neuroinflammatory effects. rV01 reduces tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion. RV01 reduced tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion, inhibited lps-induced ROS production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, decreased toll-like receptor 4 (TLR4) protein expression, and inhibited lps-induced activation of mitogen-activated protein kinase (MAPK) and nuclear transcription factor-кB (NF-кB) signaling pathways.

Semapimod tetrahydrochloride (CPSI-2364 tetrahydrochloride) is a synthetic ornithine mitogen-activated protein kinase blocker and pro-inflammatory cytokine production inhibitor that interferes with macrophage and microglia function. Sematimod tetrahydrochloride inhibits TLR4 signaling, TNF-α, IL-1β, and IL-6, and is used in the study of Crohn's disease and other inflammatory conditions.

TLR4 inhibitor. Inhibits LPS-induced NF-κB activation in HEK293 cells (IC50 = 2.4 μg/mL). Also inhibits LPS-induced cytokine production and procoagulant effects in PBMCs and HUVECs. Prolongs survival in a mouse septic shock model.

Sparstolonin B, a selective TLR2 and TLR4 antagonist, is an isocoumarin compound isolated from the tubers of Sparganium stoloniferum and Scirpus yagara with anti-HIV, anticancer, antitumour and anti-inflammatory activities, inhibits selective Toll-like receptors, inhibits free fatty acids It inhibits selective Toll-like receptors, inhibits free fatty acid palmitate-induced chondrocyte inflammation and attenuates post-traumatic arthritis in obese mice, and inhibits lipopolysaccharide-induced inflammation in 3T3-L1 adipocytes, which can be used for validation and mammary carcinoma studies.

Kdo2-Lipid A ammonium (KLA) is a selective and potent TLR4 agonist, a lipopolysaccharide.Kdo2-Lipid A ammonium induces the release of TNF and PGE2.

1. Isofraxidin (Phytodolor) protects leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in a p53-independent manner. 2. Isofraxidin has a protective effect against LPS-induced ALI, and the protective effect of Isofraxidin seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2. 3. Isofraxidin possesses significant analgesic and anti-inflammatory activities that may be mediated through the regulation of pro-inflammatory cytokines, TNF-α and the phosphorylation of p38 and ERK1/2.

Okanin shows significant activities on both linoleic acid peroxidation inhibition and DPPH radical scavenging effect.

TLR4 agonist. Promotes NF-κB nuclear translocation and induces inflammatory cytokine secretion in RAW264.7 macrophages in vitro. Acts as an adjuvant in vivo; enhances X-15 specific antibody serum concentrations, when administered with X-15-KLH in mice.

RS09 2TFA (1449566-36-2 free base) is a TLR4 agonist. Promotes NF-κB nuclear translocation and induces inflammatory cytokine secretion in RAW264.7 macrophages in vitro. It acts as an adjuvant in vivo and enhances X-15 specific antibody serum concentrations.

Alogliptin Benzoate (SYR 322)(SYR 322), an effective and specific DPP-4 inhibitor (IC50<10 nM), exhibits greater than 10, 000-fold selectivity over DPP-8/9. Alogliptin may inhibit inflammatory responses by preventing the toll-like receptor 4 (TLR-4)-mediated formation of proinflammatory cytokines.

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.

4-Octylphenol is an endocrine disruptor with gender-specific effects on male germ cells, significantly reducing the mitotic index and the number of spermatogonia. It also causes inflammatory damage in the gills of carp by activating the complement system through the C3a/C3a receptor (C3a/C3aR) axis and C5a/C5a receptor 1 (C5a/C5aR1) axis. Furthermore, 4-Octylphenol induces immune suppression by disrupting the balance between helper T (Th) cells 1/Th2 and regulatory T (Treg)/Th17 cells, and triggers inflammatory damage through the Toll-like receptor 7 (Toll-like Receptor (TLR))/inhibitor κBα/nuclear factor κB (TLR7/IκBα/NF-κB) pathway.

Givinostat (ITF-2357) is an HDAC inhibitor with IC50 values of 198 nM for HDAC1 and 157 nM for HDAC3.

TLR4-IN-C34-C2-COO is a linker compound incorporating the TLR4 inhibitor TLR4-IN-C34, effectively inhibiting TLR4 activity in enterocytes and macrophages, and mitigating systemic inflammation in murine models of endotoxemia and necrotizing enterocolitis.

TLR7/8 agonist 4 hydroxy-PEG10-acid [compound 9] is a drug-linker conjugate used in antibody-drug conjugates (ADC), exhibiting remarkable antitumor activity. It utilizes TLR7/8 agonist 4, a potent activator of TLR7/8, linked to hydroxy-PEG10-acid via a cleavable bond, demonstrating promising pharmaceutical potential in ADC-based therapeutics.

TLR7/8 agonist 4 TFA (compound 41) is a highly potent TLR7/8 agonist demonstrating significant anti-cancer activity.

TLR7/8 agonist 4 hydroxy-PEG10-acid hydrochloride (compound 9) is a drug-linker conjugate used in antibody-drug conjugates (ADCs) with high tumor efficacy. It consists of TLR7/8 agonist 4, a potent TLR7/8 agonist, linked to the ADC linker hydroxy-PEG10-acid, which can be cleaved.

Lipopolysaccharides from Escherichia coli O111:B4 are key components of the outer membrane of Gram-negative bacteria. As a smooth-type LPS, they consist of lipid A, an R3-type core oligosaccharide, and an O-specific polysaccharide. These LPS molecules exhibit high immunogenicity, can trigger strong immune responses and gastric disorders by activating the TLR-4 receptor on immune cells, and help maintain the structural integrity of the bacterial outer membrane while protecting against bile salts and lipid-based antibiotics. They are widely used to establish inflammation-related disease models, such as chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS).