tnf-a 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) 是一种肿瘤坏死因子受体拮抗剂，对 TNFα具有更高选择性。

CU-115 是一种有效的，选择性的 TLR8 拮抗剂。CU-115对 TLR8 和 TLR7的 IC50分别为1.04 µM 和=>50 µM。THP-1 细胞中，CU-115 减少了 R-848 激活的 TNF-α 和 IL-1β 的产生。

Rupatadine (UR-12592) is a potent dual PAF H1 antagonist with Ki of 0.55 0.1 uM(rabbit platelet membranes guinea pig cerebellum membranes).IC50 value:Target: PAF H1 antagonistin vitro: Rupatadine competitively inhibited histamine-induced guinea pig ileum contraction (pA2 = 9.29 + - 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 + - 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or arachidonic acid-induced platelet aggregation [1]. The IC50 for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7+ -0.4 microM, 3.2+ -0.7 microM and 1.5+ -0.4 microM, respectively whereas for loratadine the IC50 was 2.1+ -0.9 microM, 4.0+ -1.3 M and 1.7+ -0.5 microM. SR-27417A exhibited no inhibitory effect [2].in vivo: Rupatadine blocked histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 micrograms kg i.v.). Moreover, it potently inhibited PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg kg i.v.) [1]. rupatadine treatment improved the declined lung function and significantly decreased animal death. Moreover, rupatadine was able not only to attenuate silica-induced silicosis but also to produce a superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist loratadine, or PAF antagonist CV-3988 [3]. [1]. Merlos M, et al. Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF). J Pharmacol Exp Ther. 1997 Jan;280(1):114-21. [2]. Queralt M, et al. In vitro inhibitory effect of rupatadine on histamine and TNF-alpha release from dispersed canine skin mast cells and the human mast cell line HMC-1. Inflamm Res. 2000 Jul;49(7):355-60. [3]. Lv XX, et al. Rupatadine protects against pulmonary fibrosis by attenuating PAF-mediated senescence in rodents. PLoS One. 2013 Jul 15;8(7):e68631.

J-113863 是选择性的 CCR1 (CD18)拮抗剂，有抗炎作用，对人和小鼠 CCR1受体的 IC50值分别为 0.9 和 5.8 nM。它是人 CCR3的强效拮抗剂，还是小鼠 CCR3的弱效拮抗剂，IC50分别为 0.58 和 460 nM。

NCI 126224 是一种 toll-like receptor 4 (TLR4) 的拮抗剂。它在 RAW 264.7 巨噬细胞中，选择性抑制由 TLR4 激动剂 LPS 引起的一氧化氮 (NO) 产生（IC50 = 0.31 µM），而对 TLR7/8 激动剂 R-848、TLR1/2 激动剂 Pam3CSK4 以及 TLR3 激动剂 poly(I:C) 的影响较小；但对于相同细胞中由 TLR2/6 激动剂 FSL-1 引起的 NO 产生，其抑制作用在 0.6 µM 时亦显现。此外，NCI 126224 在 BV-2 微胶质细胞的报告实验中抑制了 LPS 引起的 NF-κB 活性，并在 RAW 264.7 巨噬细胞中降低了 LPS 引起的 IL-1β 和 TNF-α 水平（IC50s = 5.92, 0.42, 和 1.54 µM，分别）。

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.

JPE-1375 是一种补体C5a 受体 1 (C5aR1) 拮抗剂。JPE-1375 能有效抑制小鼠体内多形核白细胞动员 (EC50=6.9 µM) 和降低TNF 水平 (EC50=4.5 µM)。JPE-1375 可用于自身免疫性和炎性疾病的研究。

CAY10789 (化合物 6) 是有效的CysLT1R 拮抗剂 ，IC50值为2.80 μM。CAY10789 也是一种GPBAR1激动剂 ，EC50为3 μM。CAY10789 显著降低 U937 细胞对 HAEC 的粘附并降低 TNF-α 的表达。CAY10789 表现出有前途的代谢稳定性和出色的药代动力学。 CAY10789 可用于结肠炎、代谢综合征和其他 GPBAR1 CysLT1R 相关疾病的研究。

PMX-53是一种大环型补体5a (C5a) 类肽模拟物及C5a受体的拮抗剂（IC50 = 0.3 µM）。它能抑制C5a诱导的人类分离性多形核白细胞（PMNs）中的髓过氧化物酶（MPO）分泌。在大鼠腹膜亚瑟斯反应模型中，PMX-53（10 mg kg, p.o.）能够抑制血管渗漏、多形核白细胞浸润以及腹膜TNF-α和IL-6的产生。在3-硝基丙酸（3-NP）诱导的亨廷顿病大鼠模型中，它能减少体重损失和厌食，抑制纹状体退化。PMX-53（3 mg kg）还能在ApoE- -小鼠中减小动脉粥样硬化斑块大小和脂质含量。

T-5342126 is a toll-like receptor 4 (TLR4) antagonist.1It reduces LPS-induced production of nitric oxide (NO) in RAW 264.7 cells (IC50= 27.8 μM), as well as 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) 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.2 1.Chavez, S.A., Martinko, A.J., Lau, C., et al.Development of β-amino alcohol derivatives that inhibit toll-like receptor 4 mediated inflammatory response as potential antisepticsJ. Med. Chem.54(13)4659-4669(2011) 2.Bajo, M., Montgomery, S.E., Cates, L.N., et al.Evaluation of TLR4 inhibitor, T5342126, in modulation of ethanol-drinking behavior in alcohol-dependent miceAlcohol Alcohol.51(5)541-548(2016)

Theobromine-d6 is intended for use as an internal standard for the quantification of theobromine by GC- or LC-MS. Theobromine 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 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 is toxic to dogs with an LD50 value of 250 to 500 mg kg.