tnf-a , human

TNF-α (31-45), human acetate is a peptide of tumor necrosis factor-α.

Adalimumab (anti-TNF-alpha) is the first fully human recombinant IgG1 monoclonal antibody that specifically targets human TNF-alpha.

Infliximab is a monoclonal antibody, a human-mouse chimeric monoclonal antibody that inhibits TNF-α and prevents TNF-α from interacting with TNFR1 and TNFR2. Infliximab can be used to treat Crohn's disease and rheumatoid arthritis.

Cot inhibitor-1 is a selective inhibitor of Cot protein kinase (also known as Tpl2 or MAP3K8) (IC50 at 28 nM). Cot inhibitor-1 inhibited TNF-alpha production in human whole blood with IC50 of 5.7 nM. Cot is involved in a variety of cellular signaling pathways, particularly those involved in inflammation and immune responses. Cot inactivate-1 inhibits Cot activity and may have potential therapeutic effects on rheumatoid arthritis, inflammatory bowel disease and some types of cancer.

Cot inhibitor-2 is a cot (Tpl2/MAP3K8) inhibitor (IC50: 1.6 nM) with potency, selectivity and oral activity. cot inhibitor-2 inhibits LPS-stimulated TNF-α production in human whole blood with an IC50 of 0.3 μM.

3-Hydroxykynurenamine, also known as 3-Hydroxy-L-kynurenamine or 3-HKA, is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction.This compound is unstable in powder form and other related salt forms are recommended.

Ataquimast inhibits IL-5 secretion along with that of TNF-a, IL-4 and GM-CSF from human cells.

J-113863 is also a potent antagonist of the human CCR3 (IC50 of 0.58 nM) , but a weak antagonist of the mouse CCR3 (IC50 of 460 nM). J-113863 is inactive against CCR2, CCR4 and CCR5, as well as the LTB4 or TNF-α receptors. Anti-inflammatory effect. J-113863 is a potent and selective CCR1 (CD18) antagonist with IC50 values of 0.9 nM and 5.8 nM for human and mouse CCR1 receptors, respectively.

TNF-α (31-45), human, is a peptide of tumor necrosis factor-α.

MN-25 (compound 4a) is an orally active indole pyridinone that functions as a novel cannabinoid ligand. It exhibits binding affinities (Ki) of 245 nM for CB1 and 11 nM for CB2 receptors. As a CB2 agonist, MN-25 inhibits TNF-R release from human peripheral blood mononuclear cells in vitro, with an IC50 of 33 μM. However, in an acute inflammation model in mice, MN-25 did not demonstrate efficacy at oral doses up to 50 mg/kg.

hMAO-B-IN-11 (Compound 12) is a selective and reversible inhibitor of human monoamine oxidase B (hMAO-B) with an IC50 value of 0.11 µM. It operates by competitively binding to the active site of hMAO-B, thereby preventing the oxidative deamination of monoamines and reducing hydrogen peroxide production. Additionally, hMAO-B-IN-11 inhibits pro-inflammatory mediators (NO, TNF-α, IL-1β) in activated microglia. This compound holds potential for research in neurodegenerative diseases such as Parkinson's and Alzheimer's.

SMU-14a is a TLR3 inhibitor with an IC50 of 0.18 µM. It suppresses IL-6 secretion in mouse peritoneal macrophages and downregulates TNF-α in human peripheral blood mononuclear cells. The compound exerts anti-inflammatory effects by reducing the phosphorylation of p65, ERK, and TBK1 via the NF-κB, MAPK, and IRF3 signaling pathways, and by lowering serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). SMU-14a is applicable in acute hepatitis research.

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.

TLR7 agonist22 (Compound 11a) is a selective TLR7 agonist with an IC50 value of 25.86 μM. It inhibits the secretion of cell HBsAg and effectively activates TLR7, inducing the release of TLR7-regulated cytokines IL-12, TNF-α, and IFN-α in human PBMC cells. TLR7 agonist22 shows promise for developing novel immunomodulatory drugs in HBV research.

TLR7 agonist21 (Compound 27B) is a selective activator of Toll-like receptor 7 (TLR7), with an EC50 of 17.53 nM for human TLR7 and 41.7 nM for mouse TLR7. It induces the secretion of pro-inflammatory cytokines, including IL-6, TNF-α, IFN-α1, and IL-4. Acting as a vaccine adjuvant, TLR7 agonist21 enhances IgG and IgA levels, offering protection for mice against influenza virus infection.

RJG-2036 is a potent covalent inhibitor of human prostaglandin reductase 2 (PTGR2) with an IC50 of 100 nM. It effectively inhibits NADPH-dependent reduction reactions, significantly reducing the secretion of inflammatory factors such as TNF-α and the release of various pro-inflammatory eicosanoids in LPS-stimulated THP-1 macrophages. RJG-2036 shows promise for research in inflammatory diseases.

1-Arachidonoyl-2-hydroxy-sn-glycero-3-PA is a phospholipid that contains arachidonic acid at the sn-1 position, serving as a precursor to 1-Monoarachidin. It binds with the LPA2/EDG4 receptor and can inhibit the secretion of TNF-α and IL-6 induced by LPS in wild-type dendritic cells but does not affect Lpa2-/- dendritic cells. Additionally, it reduces the differentiation of HT-29 human colon cancer cells into goblet cells in the presence of sodium butyrate.

(+)-Armepavine is an active compound from Nelumbo nucifera that exhibits anti-inflammatory effects on human peripheral blood mononuclear cells, immunosuppressive effects on T lymphocytes, and protective activity in lupus nephritic mice, in part by inhibiting TNF-α-induced MAPK and NF-κB signaling pathways.

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid peptide hormone produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland, as well as in keratinocytes, astrocytes, monocytes, and gastrointestinal cells.1It is an agonist of melanocortin receptor 3 (MC3R) and MC4R that induces cAMP production in Hepa cells expressing the human receptors (EC50s = 0.16 and 56 nM, respectively).2α-MSH (100 pM) reducesS. aureuscolony formation andC. albicansgerm tube formationin vitro.3It inhibits endotoxin-, ceramide-, TNF-α-, or okadaic acid-induced activation of NF-κB in U937 cells.1α-MSH reduces IL-6- or TNF-α-induced ear edema in mice.4It also prevents the development of adjuvant-induced arthritis in rats and increases survival in a mouse model of septic shock. Increased plasma levels of α-MSH are positively correlated with delayed disease progression and reduced death in patients with HIV.1 1.Catania, A., Airaghi, L., Colombo, G., et al.α-melanocyte-stimulating hormone in normal human physiology and disease statesTrends Endocrinol. Metab.11(8)304-308(2000) 2.Miwa, H., Gantz, I., Konda, Y., et al.Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptorsJ. Pharmacol. Exp. Ther.273(1)367-372(1995) 3.Cutuli, M., Cristiani, S., Lipton, J.M., et al.Antimicrobial effects of a-MSH peptidesJ. Leukoc. Biol.67(2)233-239(2000) 4.Lipton, J.M., Ceriani, G., Macaluso, A., et al.Antiiinflammatory effect of the neuropeptide a-MSH in acute, chronic, and systemic inflammationAnn. N.Y. Acad. Sci.25(741)137-148(1994)

(S)-p38 MAPK inhibitor III is a methylsulfanylimidazole that inhibits p38 MAP kinase (IC50 = 0.90 μM in vitro). It is cell-permeable, potently blocking the release of TNF-α and IL-1β from human peripheral blood mononuclear cells (IC50s = 0.37 and 0.044 μM, respectively).

Tpl2 kinase inhibitor is an inhibitor of tumor progression locus 2 (Tpl2; IC50= 0.05 μM).1It is selective for Tpl2 over MEK, p38 MAPK, Src, MK2, and PKC (IC50s = >40, 180, >400, 110, and >400 μM, respectively). Tpl2 kinase inhibitor inhibits LPS-induced TNF-α production in isolated human monocytes and whole blood (IC50s = 0.7 and 8.5 μM, respectively). It enhances differentiation induced by calcitriol in HL-60 and U937 leukemia cells when used at a concentration of 5 μM.2Tpl2 kinase inhibitor (5 μM) inhibits the proliferation of KG-1a leukemia cells.3 1.Garvin, L.K., Green, N., Hu, Y., et al.Inhibition of Tpl2 kinase and TNF-α production with 1,7-naphthyridine-3-carbonitriles: Synthesis and structure-activity relationshipsBioor. Med. Chem. Lett.15(23)5288-5292(2005) 2.Wang, X., and Studzinski, G.P.Expression of MAP3 kinase COT1 is up-regulated by 1,25-dihydroxyvitamin D3 in parallel with activated c-jun during differentiation of human myeloid leukemia cellsJ. Steroid. Biochem. Mol. Biol.121(1-2)395-398(2010) 3.Wang, X., Gocek, E., Novik, V., et al.Inhibition of Cot1/Tlp2 oncogene in AML cells reduces ERK5 activation and up-regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle arrest induced by silibinin and 1,25-dihydroxyvitamin D3Cell Cycle9(22)4542-4551(2010)

SMU127 is an agonist of the toll-like receptor 1/2 (TLR1/2) heterodimer.

Sirtuins (SIRTs) represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs). Human SIRT1 is the homolog of yeast silent information regulator 2 (Sir2) and has been shown to regulate the activity of the p53 tumor suppressor and inhibit apoptosis. Small molecule activators of SIRT1, such as resveratrol, extend lifespan in yeast and C. elegans in a manner that resembles caloric restriction. CAY10591 has been identified as an activator of the enzyme SIRT1. This compound increases fluorescence by 233% in a SIRT1 activity assay. [Activator activity was defined as the percentage of signal increase relative to signal window in the following formula: 100 x (Sample - Signallow)/(Signalhigh - Signallow)]. CAY10591 suppresses TNF-α in a dose-dependent manner. In THP-1 cells, TNF-α levels decreased from 325 pg/ml (control) to 104 and 53 pg/ml with 20 and 60 µM CAY10591, respectively. This activator also has a significant dose-dependent effect on fat mobilization in differentiated adipocytes, which would indicate the potential of SIRT1 activators for anti-obesity or anti-diabetic purposes.

9(Z),11(E)-Conjugated linoleic acid is an isomer of linoleic acid that has been found in beef and milk fat.1It binds to peroxisome proliferator-activated receptor α (PPARα; IC50= 140 nM) and activates the receptor in a reporter assay using COS-1 cells expressing mouse PPARα when used at a concentration of 100 μM.29(Z),11(E)-Conjugated linoleic acid inhibits TNF-α-inducedGLUT4expression and increases insulin-stimulated glucose transport in 3T3-L1 adipocytes.3Dietary administration of 9(Z)11(E)-conjugated linoleic acid reduces serum fasting glucose, insulin, and triglyceride levels and decreases white adipose tissue macrophage infiltration inob/obmice. It also increases body weight gain and body fat in weanling mice.4[Matreya, LLC. Catalog No. 1278] 1.Shultz, T.D., Chew, B.P., Seaman, W.R., et al.Inhibitory effect of conjugated dienoic derivatives of linoleic acid and β-carotene on the in vitro growth of human cancer cellsCancer Lett.63(2)125-133(1992) 2.Moya-Camarena, S.Y., Heuvel, J.P.V., Blanchard, S.G., et al.Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARαJ. Lipid Res.40(8)1426-1433(1999) 3.Moloney, F., Toomey, S., Noone, E., et al.Antidiabetic effects of cis-9, trans-11-conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissueDiabetes56(3)574-582(2007) 4.Pariza, M.W., Park, Y., and Cook, M.E.The biologically active isomers of conjugated linoleic acidProg. Lipid Res.40(4)283-298(2001)