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.

R-7050 (TNF-α Antagonist III) is a tumor necrosis factor receptor (TNFR) antagonist that exhibits heightened selectivity for TNFα.

CU-115 is a selective and potent TLR8 antagonist with IC50 of 1.04 µM and =>50 µM for TLR8 and TLR7, respectively. CU-115 decreases production of TNF-α and IL-1β activated by R-848 in THP-1 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.

CB1R antagonist 2 (Compound 11g) functions as an antagonist of the cannabinoid receptor 1 (CB1R), inhibiting the MAPK/NF-κB signaling pathway and exhibiting anti-inflammatory properties. In RAW264.7 cells, it suppresses LPS-induced expression of IL-6, IL-1β, and TNF-α. In murine models, it improves OVA-induced allergic rhinitis.

Z-3578 is a small molecule antagonist targeting the MrgX2 (Mas-related G protein-coupled receptor X2) with notable anti-pseudoallergic properties, exhibiting a KD value of 729 nM. It effectively inhibits mast cell degranulation induced by substance P (SP) and C48/80, with IC50 values of 4.90 µM and 6.18 µM, respectively, suppresses the release of β-hexosaminidase, and significantly reduces the release of histamine and TNF-α, as well as intracellular calcium flux. Additionally, in a mouse pseudoallergy model, Z-3578 significantly alleviates foot swelling, dye leakage, and reduces serum histamine levels, indicating a strong in vivo anti-allergic effect. Z-3578 presents as a promising lead compound in the field of anti-allergic treatments, particularly for pseudoallergic reactions.

Compound 25l, also known as P2Y14R antagonist 4, is an orally active antagonist of the P2Y14R receptor with an IC50 of 5.6 nM. It exhibits higher binding affinity for P2Y14R compared to other PPTN receptors. P2Y14R antagonist 4 also possesses anti-inflammatory properties, reducing the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) induced by LPS.

T0080 is an FPR-1 antagonist. It reduces apoptosis (Apoptosis) and inhibits the production of reactive oxygen species (ROS) and pro-inflammatory cytokines (TNF-α and IL-1β) in plaque macrophages within ApoE−/− mouse models, thereby slowing the progression of atherosclerosis.

P2Y14R antagonist 5 (Compound A) is a novel P2Y14R antagonist with a benzisoxazole-based structure, exhibiting an IC50 of 23.60 nM and a KD of 7.26 μM. This compound can reduce levels of pro-inflammatory factors (IL-1β, IL-6, TNF-α) and myeloperoxidase (MPO). It demonstrates anti-inflammatory activity in a mouse model of LPS-induced acute lung injury.

TRPM8 antagonist 4 is a compound with high functional selectivity and favorable physicochemical properties, serving as a CB2R partial agonist (EC50=54.2 μM, Ki=3.2 μM) and a TRPM8 (IC50=42.3 nM) antagonist. It possesses notable anti-inflammatory and analgesic effects, demonstrating good safety by reducing the mRNA expression of TNF-α, IL-6, and IL-1β.

GDC-0152-acetamide is a pan-antagonist of apoptosis inhibiting proteins (IAPs). It induces the autoubiquitination and subsequent degradation of cIAP1/2, activates the non-canonical NF-κB pathway, and promotes the secretion of TNF-α, leading to apoptosis in tumor cells. GDC-0152-acetamide holds potential for research in ERα-positive breast cancer.

SMU-R39 is a TLR7 and TLR8 antagonist with IC50 values of 3.22 μM and 0.24 μM, respectively. It binds to recombinant mTLR7 protein (KD= 2.36 μM) and recombinant hTLR8 protein (KD= 105 nM). SMU-R39 inhibits downstream NF-κB and MAPK signaling pathways, reducing the secretion and transcription of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in PBMCs and THP-1 cells. In an Imiquimod (IMQ)-induced psoriasis mouse model, SMU-R39 exhibits anti-inflammatory activity and may be used for researching autoimmune diseases such as psoriasis.

NPSR1 antagonist-1 is a potent and peripherally restricted antagonist of the neuropeptide S receptor 1 (NPSR1). It can inhibit the expression of IL-6, PTGS2, IL-20, and CXCL8, and it also reduces TNF-α cytokine levels. NPSR1 antagonist-1 is useful in inflammation-related research, such as peritonitis studies.

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.

TG6-129 is an antagonist of the EP2 receptor. TG6-129 suppresses PGE2-induced elevation of cAMP in cells expressing EP2 with an IC50 value of 1.6 µM. TG6-129 reduces the expression of COX-2, IL-1β, IL-6, IL-12, IL-23 and TNF-α induced by the EP2-selective

T-5342126 is a toll-like receptor 4 (TLR4) antagonist that reduces LPS-induced production of nitric oxide (NO) in RAW 264.7 cells (IC50 = 27.8 μM) and decreases LPS-induced IL-8, TNF-α, and IL-6 production in isolated human whole blood (IC50s = 110.5, 315.6, and 318.4 μM, respectively). T-5342126 (82 mg/kg) also reduces ethanol intake and the abundance of ionized calcium-binding adapter molecule 1 (Iba1), a marker of microglial activation, in the central nucleus of the amygdala in ethanol-dependent mice.

ISO-1 (MIF Antagonist) is an inhibitor of the dopachrome tautomerase activity, blocks the activation of NF-κB and TNF-α secretion from LPS-treated macrophages.

R-8507 is a small molecule antagonist of the TNF-α type 1 receptor (TNF-αRI). It inhibits the expression of intercellular adhesion molecule-1 (ICAM-1) induced by TNF-α and IL-1β with EC50 values of 2.45 and 3.79 μM, respectively, in an ELISA using A549 lung epithelial cells.{|Gururaja2007|} It also disrupts the interaction of the TNF-αRI with receptor interacting protein 1 (RIP1) and TNF-αR-associated death domain protein (TRADD), preventing internalization of the receptor complex.

CAY10789 (compound 6) is a potent CysLT1R (cysteinyl leukotriene receptor 1) antagonist with an IC50 of 2.80 μM and a GPBAR1 (G-protein-coupled bile acid receptor 1) agonist with an EC50 of 3 μM. It significantly decreases U937 cell adhesion to HAEC and reduces TNF-α expression. CAY10789 demonstrates promising metabolic stability and excellent pharmacokinetics, making it suitable for studying colitis, metabolic syndromes, and other GPBAR1/CysLT1R-related diseases [1].

NOD2 antagonist 1 (compound 32) is a selective NOD2 antagonist (IC50=5.23 μM) that inhibits MDP-induced IL-8 secretion in THP-1 cells and suppresses MDP-induced IL-6, IL-10, and TNF-α in PBMCs.

Theobromine-D6 is intended for use as an internal standard for the quantification of theobromine by GC- or LC-MS. Theobromine (T0625) is a methylxanthine alkaloid and derivative of caffeine that has been found in cocoa beans and has diverse biological activities. It is an adenosine A1 receptor antagonist. Theobromine (T0625) increases AMPK phosphorylation and inhibits adipocyte differentiation, ERK and JNK phosphorylation, and IL-6 and TNF-α production in 3T3-L1 preadipocytes cultured in differentiation medium. It inhibits decreases in renal cortex SIRT1 activity and increases in NADPH oxidase-dependent reactive oxygen species (ROS) production, as well as reduces kidney hypertrophy and albuminuria in a spontaneously hypertensive rat model of streptozotocin-induced diabetes when administered at a dose of 5 mg/kg per day.3 Theobromine (T0625) is toxic to dogs with an LD50 value of 250 to 500 mg/kg.

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.

LASSBio-1135 is an orally effective antagonist of TRPV1 and inhibitor of TNF-α production.