TNF-α-IN-10

TNF-α-IN-10 (compound 8a) is an inhibitor of IL-6 and TNF-α, exhibiting anti-inflammatory activity [1].

LTβR-IN-1 is a potent and selective lymphin β receptor (LTβR) inhibitor with a selective inhibitory effect on the nuclear translocation of p52 of TNF12A, without affecting the nuclear translocation of p65 mediated by the TNF-α receptor. It inhibits p52 nuclear translocation stimulated by TWEAK or Anti-LTβR with an IC50 of 10 μM and regulates the NF-kB signaling pathway in a ligand-independent manner.

CU-T12-9 is a potent TLR1/2 agonist(EC50 of 52.9 nM in HEK-Blue hTLR2 SEAP assay). It acts by activating the NFkB pathway, upregulating proinflammatory cytokines, and enhancing TLR1 and TLR2 dimerization.CU-T12-9 activates both the innate and the adaptive immune systems. CU-T12-9 selectively activates the TLR1/2 heterodimer, not TLR2/6. CU-T12-9 signals through NF-κB and invokes an elevation of the downstream effectors TNF-α, IL-10, and iNOS.

TC13172 is a potent and covalent inhibitor that specifically targets the mixed lineage kinase domain-like protein (MLKL), exhibiting significant selectivity for MLKL over the closely related receptor-interacting serine/threonine kinase 1 (RIPK1) and RIPK3 at a concentration of 10 µM.TC13172 effectively inhibits necroptosis induced by the TSZ combination (TNF-α, a Smac mimetic, and Z-VAD-FMK) in HT-29 cells with a EC50 of 2 nM and, at 100 nM, blocks TSZ-induced oligomerization and plasma membrane translocation of MLKL.

LZ-07 is an IRAK4 PROTAC degrader (DC50 = 1.14 nM), that, upon degradation of IRAK4, significantly inhibits the expression of cytokines such as IL-6, IL-1β, TNF-α, and IL-10. It is applicable in research related to autoimmune diseases.

RIPK1-IN-29 (Compound 22) is a RIPK1 inhibitor with an IC50 of 6.9 nM. It exhibits anti-necroptotic apoptosis activity by inhibiting RIPK1. In a TNF-α induced inflammatory in vivo model, a 10 mg/kg dose of RIPK1-IN-29 can protect mice from hypothermia and death. This compound is suitable for research in the field of inflammatory diseases.

12-Nitrolinoleate is a linoleic acid derivative that acts as an agonist of peroxisome proliferator-activated receptor γ (PPARγ). Formed via exposure to acidified nitrite, it is present in human red blood cells and plasma. This compound stimulates PPARγ-dependent gene expression, demonstrated in a reporter assay with MCF-7 cells expressing human PPARγ, with an EC50 of 0.045 µM. At 2.5 µM, 12-Nitrolinoleate reduces the secretion of IL-6, TNF-α, and chemokine (C-C motif) ligand 2 (CCL2) in THP-1 and RAW 264.7 macrophages, and it suppresses LPS-induced NF-κB transcriptional activity in RAW 264.7 macrophages. Additionally, it inhibits TNF-α-induced increases in vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and enhances heme oxygenase-1 (HO-1) levels in primary human aortic endothelial cells at concentrations of 1, 5, or 10 µM.

Vasoactive intestinal peptide is an agonist of VPAC1/VPAC2 receptors (G protein-coupled receptors). In a model of Pseudomonas aeruginosa-induced keratitis, it reduces corneal perforation rates, decreases bacterial load, and inhibits excessive neutrophil infiltration. It enhances anti-inflammatory mediators such as IL-10 and TGF-β while suppressing pro-inflammatory factors like IL-1β and TNF-α, and upregulates lipid mediator-related enzymes (SOCS3, COX-2, ALOX12) to facilitate inflammation resolution. Vasoactive intestinal peptide shows promise for the research of ocular infectious diseases.

1-Arachidonoyl-2-hydroxy-sn-glycero-3-PA (sodium) [1-Arachidonoyl-sn-glycerol 3-phosphate (sodium)] is a phospholipid containing arachidonic acid at the sn-1 position. It binds to the LPA2/EDG4 receptor with an EC50 of 10 nM and is present in the rat brain, representing 37% of arachidonic acid lysophosphatidic acid species. This compound serves as a precursor to 1-arachidonoyl-sn-glycerol and inhibits the secretion of TNF-α and IL-6 from dendritic cells stimulated by wild-type LPS. Additionally, 1-arachidonoyl-2-hydroxy-sn-glycero-3-PA (sodium) can suppress the differentiation of HT-29 colon cancer cells into goblet cells in the presence of sodium butyrate.

Salicylate choline is a derivative of Aspirin (acetylsalicylic acid) and is orally active. It significantly reduces the levels of IL-1β, IL-6, TNF-α, and IL-10 in cells. By inducing S phase cell cycle arrest and impairing DNA damage repair, salicylate choline enhances the antitumor activity of the CRM1 inhibitor Selinexor (KPT-330). When combined with Selinexor, salicylate choline demonstrates excellent antitumor efficacy in mouse xenograft models with JeKo-1 cells. It is applicable in the research of rheumatism, inflammation, and cancer.

TFAM activator 1 (Compound 2) is a mitochondrial transcription factor A (TFAM) activator with anti-inflammatory properties and the ability to repair mitochondrial dysfunction. It enhances TFAM protein levels and mitochondrial DNA copy number, inhibits mitochondrial DNA-induced inflammatory responses by preventing mitochondrial DNA from escaping into the cytosol, thereby reducing cytokine production (TNF-α, CXCL-10, and IFN). Additionally, it significantly raises ATP levels, decreases fibrosis markers, and strengthens Treg 240 function. TFAM activator 1 is useful for investigating mitochondrial dysfunctions, such as those in Parkinson's and Alzheimer's disease.

TNF-α-IN-27 (Compound 1) is a TNF-α inhibitor with a 64% inhibition rate at a concentration of 10 μM. It is applicable in research related to inflammation and immunology, including studies on asthma.

rel-(1S,2R)-Dihydro bupropion is a metabolite of bupropion. It enhances the production of endogenous IL-10 and inhibits Th1 cytokines (IL-12 and TNF-α), which induces a shift in the immune response from Th1 to Th2. This compound can be utilized in the study of inflammatory diseases.

AHR agonist 10 is a potent activator of the AHR pathway (EC50 = 2.01 nM). It enhances transcription of key downstream target genes of AHR, such as CYP1A1 and CYP1B1, while reducing the expression of CD36 and IL-18, and demonstrates low cytotoxicity in normal cells (> 40 μM). This compound inhibits the expression of CCL5, CCL20, IL-6, IL-8, S100A9, TLR4, TNF-α, and TNFR1, indicating its effective regulation of inflammatory responses via AHR-dependent signaling. AHR agonist 10 is applicable in psoriasis research [1].

CT-133 is a selective and potent antagonist of the CRTH2 Receptor, with a Ki value of 2.2 nM, and exhibits a Ki greater than 3800 nM for the DP1 receptor. It inhibits PGD2-induced neutrophil migration and significantly reduces lung inflammation and improves lung function impairment in a mouse model of acute lung injury (ALI) induced by cigarette smoke. Additionally, CT-133 effectively suppresses the overexpression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and the chemokine (KC) while reversing the suppression of the anti-inflammatory factor IL-10. CT-133 is useful for ALI research.

Multi-target kinase-IN-10 (Compound 6l) is an orally active, brain-penetrant, selective, reversible, and competitive MAO-B inhibitor with an IC50 of 0.0053 μM. It competes with substrates for binding to the active site of MAO-B, chelates Cu2+ ions, inhibits Cu2+-induced ROS production, and decreases the release of NO, TNF-α, and IL-1β. Multi-target kinase-IN-10 shows potential for improving Parkinson's disease.

JTE-607 is a cytokine production inhibitor. JTE-607 induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells.

17(R)-Protectin D1 is an aspirin-triggered epimer of the specialized pro-resolving mediator protectin D1 .1It decreases leukotriene B4-induced transendothelial migration of human polymorphonuclear (PMN) neutrophils when used at concentrations ranging from 0.1 to 10 nM. 17(R)-Protectin D1 (0.01-10 ng) reduces the recruitment of neutrophils in a mouse model of TNF-α-induced peritonitis. 1.Serhan, C.N., Fredman, G., Yang, R., et al.Novel proresolving aspirin-triggered DHA pathwayChem. Biol.18(18)976-987(2011)

Rhein-13C4 is intended for use as an internal standard for the quantification of rhein by GC- or LC-MS. Rhein (T2997) is an anti-inflammatory anthraquinone found in rhubarb and is the bioactive derivative of its prodrug diacerein . At 10 μM, rhein inhibits IL-1β signaling, suppressing signaling through NF-κB, and reduces the expression of the matrix metalloproteases MMP-1 and MMP-13.1 It inhibits IKKβ (IC50 = 11.8 μM), decreasing iNOS and IL-6 expression in LPS-stimulated macrophages but paradoxically increasing TNF-α, IL-1β, and HMBG1 expression.2 Rhein (T2997) shows efficacy against pancreatic fibrosis, chronic pancreatitis, and hyperglycemia-induced pancreatic β-cell apoptosis.3,4 It also inhibits angiogenesis of breast cancer cells under normoxic and hypoxic conditions.5

1-Arachidonoyl lysophosphatidic acid is a phospholipid containing arachidonic acid at the sn-1 position. It has been found in rat brain as 37% of the arachidonic acid-containing lysophosphatidic acid (LPA) species and is a precursor to 1-arachidonoyl glycerol . 1-Arachidonoyl lysophosphatidic acid binds to the LPA2/EDG4 receptor with an EC50 value of approximately 10 nM. It prevents TNF-α and IL-6 secretion in wild-type but not Lpa2-/- dendritic cells stimulated by LPS. It also decreases differentiation of HT-29 human colon carcinoma cells to goblet cells in the presence of sodium butyrate.

Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM and an IC50 value of 0.109 μM. It tightly binds to TNF-α, blocking its interaction with TNFR1, and has potential for TNF-α mediated inflammatory and autoimmune disease research [1].

Pyranonigrin A is a fungal metabolite originally isolated from Aspergillus that has antioxidant activity. It scavenges 2,2-diphenyl-1-picrylhydrazyl (DPPH;) free radicals in a cell-free assay (IC50 = 132.9 μM). Pyranonigrin A (10 μM) suppresses TNF-α-induced expression of vascular cell adhesion molecule 1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs).

Resveratrol-3-O-sulfate is a metabolite of resveratrol . In U-937 cells stimulated with LPS, resveratrol-3-O-sulfate (1 μM) decreases the expression of IL-1α, IL-1β, and IL-6 by 61.2, 76.6, and 42.2%, respectively, and decreases the release of TNF-α and IL-6 to similar levels as resveratrol. It has antioxidant activity in a Trolox assay, dose-dependently decreases growth of Caco-2 colorectal adenocarcinoma cells when used at concentrations ranging from 10 to 100 μM, and induces apoptosis at concentrations of 25 and 50 μM. Resveratrol-3-O-sulfate also displaces rosiglitazone from the outer mitochondrial protein mitoNEET (IC50 = 3.36 μM for the human protein), indicating that it binds to the thiazolidine-2,4-dione (TZD) binding pocket.

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