il-25

Anti-IL-25 Antibody 是在CHO细胞中表达的人源抗体，靶向IL-25。同型对照可参考Human IgG1 kappa, Isotype Control。

Anti-Mouse IL-25 Antibody (2C3) 是一种来源于小鼠的IgG1, κ型抗体抑制剂，专门用于对抗小鼠IL-25。

NLRP3-IN-25（compound 32）为口服有效的NLRP3抑制剂，表现出抗炎作用。该化合物能缓解阿霉素诱发的小鼠肾小球肾炎所导致的肾脏损伤。在THP-1细胞中，NLRP3-IN-25抑制IL-1β分泌的IC50值达21 nM。

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)

STINGagonist-25 (CF505) 是一种非核苷酸小分子 STING 激动剂。STINGagonist-23 激活 STING，增加 STING、TBK1和 IRF3的磷酸化。STINGagonist-23 可促进肿瘤细胞中IFN-β、IL-6、CXCL-10、TNF-α、ISG-15和CCL-5的水平。STINGagonist-23 表现出抗SARS-CoV 系列的活性。

RO2959 Hydrochloride (RO2959 HCl) 是选择性CRAC 通道抑制剂，IC50为 402 nM。它是人IL-2产生的有效抑制剂，有效阻断 T 细胞受体触发的基因表达和 T 细胞功能途径。它是由Orai1 Stim1通道介导的钙存储进入的有效阻滞剂，IC50为 25 nM。

Keap1-Nrf2-IN-25 (Compound 19) 是一种强效的Keap1-Nrf2抑制剂，IC50值为0.55 μM，并展现出与Keap1的结合亲和力，Kd为0.50 μM。Keap1-Nrf2-IN-25 能激活Nrf2，降低ROS及促炎细胞因子如IL-1β和IL-6的水平，对DSS诱导的结肠炎具有保护作用。

NX-2127 (ETX2514 Triethylamine) 是一种口服有效的 BTK 抑制剂，可诱导细胞中突变的 BTKC481S 降解。NX-2127 具有有效的抗增殖活性，可抑制 BTKC481S 突变体 TMD8 细胞的增殖。NX-2127 有效催化 Ikaros (IKZF1) 和 Aiolos (IKZF3) 降解，作用浓度分别为 25 nM 和 54 nM。NX-2127 与免疫系统有关，刺激 T 细胞活化并增加原代人 T 细胞中 IL-2 的产生。

GNE-3500 is a Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C (RORc or RORγ) Inverse Agonist. Retinoic acid receptor-related orphan receptor C (RORc, RORγ, or NR1F3) is a nuclear receptor that plays a major role in the production of interleukin (IL)-17. Considerable efforts have been directed toward the discovery of selective RORc inverse agonists as potential treatments of inflammatory diseases such as psoriasis and rheumatoid arthritis. GNE-3500 possessed favorable RORc cellular potency with 75-fold selectivity for RORc over other ROR family members and >200-fold selectivity over 25 additional nuclear receptors in a cell assay panel. The favorable potency, selectivity, in vitro ADME properties, in vivo PK, and dose-dependent inhibition of IL-17 in a PK PD model support the evaluation of GNE3500 in preclinical studies (J. Med. Chem., 2015, 58 (13), pp 5308–5322)

PROTAC BTK Degrader-13 (Compound 25) 是一种专门靶向BTK的PROTAC降解剂，具有DC50为0.27 μM的活性。该化合物对BTK的抑制作用IC50值为0.44 μM，并对IL-2诱导的T细胞激酶（ITK）显示IC50为2.16 μM的抑制活性。同时，PROTAC BTK Degrader-13 能抑制p38 MAPK信号通路，阻止BCR（B细胞受体）信号通路被激活。(Pink: ligand for target protein BTK ligand 15; Black: linker; Blue: ligand for E3 ligase cereblon)

Lauric acid-13C is intended for use as an internal standard for the quantification of lauric acid by GC- or LC-MS. Lauric acid is a medium-chain saturated fatty acid. It has been found at high levels in coconut oil.1Lauric acid induces the activation of NF-κB and the expression of COX-2, inducible nitric oxide synthase (iNOS), and IL-1α in RAW 264.7 cells when used at a concentration of 25 μM.2

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg kg), there is a 22% reduction for 1 mg kg and 40% for 5 mg kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

JAK-IN-25（化合物19）是一种高效的JAK抑制剂，对TYK2、JAK1、JAK2和JAK3的IC50值分别为6 nM、21 nM、8 nM、1051 nM。该化合物还能抑制人全血中IL-12（HEB IL-12），IC50为28 nM，显示其在癌症研究中的潜在应用价值。

Pap12-6是一种从蝶类P. xuthus幼虫中发现的papiliocin十二个N-端氨基酸衍生的抗菌肽。它对包括E. coli、P. aeruginosa和S. syphimurium在内的八种革兰氏阴性细菌（MIC50s = 4-8 µM）以及革兰氏阳性细菌S. aureus、耐甲氧西林的S. aureus 3126（MRSA-3126）、B. subtilis和S. epidermidis（MIC50s = 4-8 µM）具有活性，但在25 µM浓度下不影响人类红细胞、小鼠RAW 264.7巨噬细胞、人类HaCaT角质形成细胞或人类HEK293肾细胞的活性。Pap12-6在4和8 µM浓度下可引起E. coli的膜去极化。Pap12-6（10 µM）预处理可降低LPS刺激的RAW 264.7巨噬细胞中一氧化氮（NO2-）、Tnf-α和Il-6的分泌水平。在体内，Pap12-6（10 mg/kg）可以提高感染E. coli的小鼠的存活率，并且在剂量为1 mg/kg时减少感染E. coli小鼠的肺、肝和肾中菌落形成单位（CFUs）的数量。Pap12-6（1 mg/kg）在E. coli诱导的败血症小鼠模型中降低血清天门冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平及血尿素氮水平。

AF 12198 Acetate 是一种新型的低分子量 IL-1 拮抗剂。

Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM. Benpyrine tightly binds to TNF-α and blocks its interaction with TNFR1, with an IC50 value of 0.109 μM. Benpyrine has the potential for TNF-α mediated inflammatory and autoimmune disease research[1]. Benpyrine (5-20 μM; 14 hours; RAW264.7 cells) pretreatment results in a dose-dependent decrease in the phosphorylation of IκBα in RAW264.7 cells (stimulated with 10 ng mL TNF-α or 1 μg mL LPS). Benpyrine abolishes the TNF-α-induced nuclear translocation of NF-κB p65 in RAW264.7 cells[1].Benpyrine only blocks cell death induced by TNF-αWT and Y119A, and increases the cell survival rate up to 80%. Benpyrine does not obviously affect L57A- and Y59L-induced cytotoxicity in L929 cells[1]. Benpyrine (25-50 mg kg; oral gavage; daily; for 2 weeks; Balb c mice) treatment significantly relieves the symptoms of collagen-induced arthritis. Benpyrine dose-dependently decreases the levels of proinflammatory cytokines, such as IFN-γ, IL-1β and IL-6, and increases the concentration of the anti-inflammatory cytokine IL-10[1].Endotoxemia murine model shows that Benpyrine (25 mg kg) could attenuate TNF-α-induced inflammation, thereby reducing liver and lung injury[1]. [1]. Weiguang Sun, et al. Discovery of an Orally Active Small Molecule TNF-α Inhibitor. J Med Chem. 2020 Jul 15.

(±)19(20)-EDP ethanolamide is an ω-3 endocannabinoid epoxide and cannabinoid (CB) receptor agonist (EC50s = 108 and 280 nM for CB1 and CB2, respectively). It is produced through direct epoxygenation of docosahexaenoyl ethanolamide by cytochrome P450 (CYP) epoxygenases. (±)19(20)-EDP ethanolamide (25 μM) reduces the viability of 143B metastatic osteosarcoma cells. It decreases the production of IL-6 and increases the production of IL-10 when used at concentrations ranging from 2.5 to 10 μM in BV-2 microglia stimulated by LPS and decreases LPS-induced cytotoxicity when used at concentrations ranging from 5 to 10 μM. It also decreases nitrite production when used at a concentration of 7.5 μM, an effect that can be partially reversed by the CB2 receptor antagonist AM630 and the PPARγ antagonist GW 9662 . (±)19(20)-EDP ethanolamide induces vasodilation of isolated preconstricted bovine coronary arteries (ED50 = 1.9 μM) and reduces tube formation by human microvascular endothelial cells (HMVECs) in a Matrigel assay.

PapRIV是最初从B. cereus分离出的一种群体感应七肽。它被转译为一个48-氨基酸多肽，由NprB蛋白酶在细胞外分泌和加工形成活性七肽。PapRIV（1-25 µM）在BV-2微胶质细胞中诱导IL-6和TNF-α的产生，并促使NF-κB转移。

Cytogenin（一种源自S. eurocidicum的香豆素衍生物）具有多种生物活性。在每日给药25 mg/kg剂量下，能减轻Ehrlich鼠自发性腺癌模型的肿瘤重量。在体内，Cytogenin（每日30和100 mg/kg）可减少链脲佐菌素诱导的体重下降和血浆葡萄糖水平上升，以及小鼠糖尿病模型中巨噬细胞胰腺浸润。同时，在每日100 mg/kg的剂量下，能降低小鼠巨噬细胞中zymosan和LPS诱导的一氧化氮产生，及LPS诱导的Il-6水平增加。

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.

NLRP3-IN-20（compound 11）是一款口服活性的NLRP3炎症小体抑制剂，其抑制IL-1β分泌的IC50值为25 nM。该化合物展现出卓越的药代动力学性质，并在非酒精性脂肪性肝炎、致命性感染性休克以及结肠炎模型中证明了其显著疗效。