tnf α antagonist

TNF-α antagonist is an exocyclic peptide that mimics the critical TNF-α recognition loop on TNF receptor I complex and, thus, prevents ligand interaction with the receptor. By blocking the TNF receptor ligand contact site, this peptide interferes with both activating receptor activator of NF-κB (RANK) and TNF-α's recruitment and activation of osteoclasts. TNF-α antagonist has been used to block bone resorption in the study of systemic bone loss in rheumatoid arthritis and inflammatory bone destruction.

PMX-53, a macrocyclic complement 5a (C5a) peptidomimetic and C5a receptor antagonist (IC50 = 0.3 µM), effectively inhibits the C5a-induced secretion of myeloperoxidase (MPO) in isolated human polymorphonuclear leukocytes (PMNs). Administered orally at 10 mg/kg, PMX-53 mitigates vascular leakage, PMN infiltration, and the production of TNF-α and IL-6 in a rat peritoneal Arthus reaction model. Additionally, in a 3-nitropropionic acid (3-NP)-induced Huntington's disease rat model, it alleviates body weight loss, anorexia, and striatal degeneration. Furthermore, at a dose of 3 mg/kg, PMX-53 decreases atherosclerotic lesion size and lipid content in ApoE-/- mice.

NCI 126224 is a Toll-like receptor 4 (TLR4) antagonist that selectively inhibits nitric oxide production induced by the TLR4 agonist LPS in RAW 264.7 macrophages (IC50 = 0.31 µM), while exhibiting weaker effects against the TLR7/8 agonist R-848, TLR1/2 agonist Pam3CSK4, and TLR3 agonist poly(I:C). NCI 126224 also inhibits FSL-1-induced NO production at 0.6 µM and suppresses LPS-induced NF-κB activity in BV-2 glial cells, while reducing IL-1β and TNF-α levels in RAW 264.7 cells (IC50s of 5.92 and 1.54 µM, respectively). 0.42, and 1.54 µM, respectively), demonstrating its significant value in studies of inflammatory and innate immune signaling pathways.

Hydrostatin-TL1 (H-TL1) is a nonapeptide that acts as a TNF-α antagonist. This compound can be isolated from the venom glands of the sea snake Hydrophis cyanocinctus. H-TL1 competitively inhibits the interaction between TNF-α and TNFR1, thus reducing TNF-α cytotoxicity and inflammatory responses. It is applicable for research into TNF-α-related inflammatory diseases such as rheumatoid arthritis, osteoporosis, and inflammatory bowel disease (IBD).