TLR4 Inhibitor

Resatorvid (TAK-242) is a selective Toll-like receptor 4 (TLR4) inhibitor. Resatorvid inhibits NO, TNF-α and IL-6 production with IC_50s of 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid downregulates expression of TLR4 downstream signaling molecules MyD88 and TRIF. Resatorvid inhibits autophagy and plays pivotal role in various inflammatory diseases.

Chymotrypsin (EC 3.4.21.1; Chymotrypsin A) is an orally effective inhibitor targeting molecules such as TLR4, NF-κB, MMP-1, TNF-α, IL-1β, and IL-6. Chymotrypsin downregulates the TLR4/NF-κB signaling pathway, inhibiting the release of inflammatory factors, reducing cell infiltration and tissue damage. It also reduces the expression of tumor cell adhesion molecules (such as CD44 and CD54) and can be specifically detected by fluorescent probes (such as NBD-3). Chymotrypsin has anti-inflammatory, hepatoprotective, joint damage-reducing, liver protection against lipotoxicity, and anti-tumor metastasis functions. It can be used in research on diseases such as rheumatoid arthritis, non-alcoholic fatty liver disease, and melanoma metastasis. Chymotrypsin can be used in studies of inflammation, edema, and expectoration.

Thiamine hydrochloride (Thiamine chloride hydrochloride) is an essential micronutrient needed as a cofactor for many central metabolic enzymes.Thiamine hydrochloride activates NrF-2/HO-1 and inhibits TLR4, NF-κB. Thiamine hydrochloride has neuroprotective and anti-inflammatory effects. Thiamine hydrochloride can be used in the studys of diabetic complications, neurological diseases, cancers, and colitis.

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

Chymotrypsin (EC 3.4.21.1; Chymotrypsin A) (MS grade) is an orally effective inhibitor targeting molecules such as TLR4, NF-κB, MMP-1, TNF-α, IL-1β, and IL-6. Chymotrypsin (MS grade) downregulates the TLR4/NF-κB signaling pathway, inhibits the release of inflammatory factors, reduces cell infiltration and tissue damage, and also reduces the expression of tumor cell adhesion molecules (such as CD44 and CD54). It can also be specifically detected by fluorescent probes (such as NBD-3). Chymotrypsin (MS grade) has anti-inflammatory, hepatoprotective, joint damage-reducing, liver protection against lipotoxicity, and anti-tumor metastasis functions, and can be used in the research of diseases such as rheumatoid arthritis, non-alcoholic fatty liver disease, and melanoma metastasis. Chymotrypsin (MS grade) can be used in studies of inflammation, edema, and expectoration.

(R)-Balcinrenone ((R)-AZD9977) is an isomer of Balcinrenone (HY-120274). Balcinrenone is an orally active mineralocorticoid receptor modulator. Balcinrenone regulates mineralocorticoid receptor activity, inhibits aldosterone-induced target gene expression, and suppresses the activities of renal Toll-like receptor 4, MyD88 and NF-κB. Balcinrenone alleviates renal extracellular matrix remodeling, inflammatory cell infiltration, and the expression of renal injury markers. Balcinrenone restores myocardial perfusion reserve, regulates potassium homeostasis, and induces fecal potassium excretion. Balcinrenone is applicable to research on metabolism-related chronic kidney disease and heart failure.

Schaftoside is a flavonoid found in a variety of Chinese herbal medicines, such as Eleusine indica. Schaftoside inhibits the expression of TLR4 and Myd88. Schaftoside also decreases Drp1 expression and phosphorylation, and reduces mitochondrial fission.

Physcion (Parietin), an anthraquinone derivative derived from the traditional Chinese medicine rhubarb, is an effective oral active 6-phosphogluconate dehydrogenase inhibitor with blood-brain barrier permeability, with IC₅₀ and K_d values of 38.5 μM and 26.0 μM, respectively. Additionally, Physcion is an inhibitor of the <>bTLR4/NF-κB signaling pathway, exhibiting anti-inflammatory, antibacterial, and anticancer effects, and can induce Apoptosis and Autophagy in cancer cells.

Okanin, effective constituent of the flower tea Coreopsis tinctoria, attenuates LPS-induced microglial activation through inhibition of the TLR4/NF-κB signaling pathways.

Robinin is a flavonoid that can be extracted from the leaves of purple cowpea, inhibiting TGF-β, TLR4/NF-κB and TLR2-PI3k-AKT signaling pathways. Robinin exerts anti-inflammatory and anti-tumor effects. The combination of Robinin and Methotrexate (HY-14519) reduces inflammation in experimental arthritis, Robinin can decrease the Doxorubicin (HY-15142A) induced cardiac toxicity effect.

Teneligliptin (MP-513) hydrobromide hydrate is an orally active and selective dipeptidyl peptidase 4 (DPP-4) inhibitor (IC₅₀s: 0.37 and 0.29 nM for the human and rat DPP-4, respectively). Teneligliptin hydrobromide hydrate improves blood glucose levels and can be used in researches related to type 2 diabetes mellitus.

Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits MMP-7 expression and cell invasion of human hepatoma cells. Isofraxidin inhibits the phosphorylation of ERK1/2 in hepatoma cells. Isofraxidin attenuates the expression of iNOS and COX-2, Isofraxidinalso inhibits TLR4/myeloid differentiation protein-2 (MD-2) complex formation.

Guluronic acid (G2013) sodium is an orally active oxidative stress regulator and anti-inflammatory agent that exerts pharmacological effects by down-regulating various pro-inflammatory and oxidative stress-related genes (such as TLR4, NF-κB, iNOS, etc.) and inhibiting the activities of COX-2, MMPs and VEGF. Low-dose Guluronic acid sodium up-regulates the expression of immunoregulatory genes SHIP1 and SOCS1, thereby effectively inhibiting cancer-related inflammation, tumor angiogenesis, cell adhesion and metastasis, while reducing the accumulation of immunosuppressive cells. Guluronic acid sodium significantly prolongs the survival time of tumor-bearing hosts within a concentration range without direct cytotoxicity, demonstrating favorable safety. Guluronic acid sodium has involved in the research of multiple sclerosis, ankylosing spondylitis, breast cancer and other inflammatory diseases.

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.

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.

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).

L6H21, a Chalcone (HY-121054) derivative, is an orally active, potent and specific myeloid differentiation 2 (MD-2) inhibitor. L6H21 directly binds to MD-2 protein with a high affinity and low K_D value of 33.3 μM, blocking the formation of the LPS-TLR4/MD-2 complex. L6H21 inhibits LPS-induced expression of TNF-α and IL-6 in RAW264.7 macrophages, with IC₅₀ values of 6.58 and 8.59 μM, respectively. L6H21 can be used for alcoholic liver disease, metabolic disturbance and neuroinflammation research.