adjuvant-induced

Trametinib (GSK1120212) 是一种 MEK 抑制剂，抑制 MEK1 和 MEK2 (IC50=0.7/0.9 nM)，具有 ATP 非竞争性和口服活性。Trametinib 可以激活自噬，诱导凋亡。

Trametinib (DMSO solvate) (GSK-1120212 (DMSO solvate)) 是一种口服有效的 MEK 抑制剂，抑制 MEK1 和 MEK2 的 IC50分别为 2 nM。它还能激活自噬，诱导凋亡。

AP-18 是选择性的 TRPA1 抑制剂。AP-18 可以抑制 50 μM 肉桂醛诱导的 TRPA1 激活，在小鼠和人中的 IC50 分别为 4.5 μM 和 3.1 μM。AP-18 可以逆转 CFA 诱导的小鼠机械性痛觉过敏。AP-18 可以浓度依赖的方式减弱 30 μM AITC 诱导的 Yo-Pro 摄取(IC50= 10.3 μM)。

Folinic acid (Leucovorin) 是一种可用于治疗甲氨蝶呤的生物叶酸，通常与 Methotrexate (MTX) 联用来降低 MTX 诱导的毒性，可用于辅助治疗结肠癌。

Fendosal (HP-129) 是一种非甾体抗炎药。在预防性和治疗性辅助诱导的慢性炎症多关节炎模型中，它的活性是阿司匹林的 6.9 至 9.5 倍。

Met-RANTES (human) acetate 为Met-RANTES (human)的醋酸盐版本，它是CCR1和CCR5的有效拮抗剂。该化合物能够抑制人类趋化因子MIP-1α和MIP-1β，其IC50值分别为5 nM和2 nM。此外，Met-RANTES (human) acetate 也能减缓骨质破坏及缓解大鼠佐剂诱导的关节炎(AIA)的症状。

A-889425 是一种口服选择性TRPV1受体拮抗剂，其 IC50 值为335 nM（大鼠）和34 nM（人）。该化合物能有效渗透中枢神经系统，能减轻机械性异常痛，并降低脊髓神经元对 Complete Freund's adjuvant 引起的炎症大鼠后爪机械刺激的敏感性。

Cofpropamine 作为一种源自咖啡因的衍生物，能抑制多聚腺苷酸化。在大鼠的佐剂性关节炎和小鼠的胶原性关节炎模型中，它能增强Cyclophosphamide的抑制效果。

BI-113823是一种可口服的选择性缓激肽B1受体拮抗剂。在大鼠实验中，BI-113823能够缓解完全弗氏佐剂（Complete Freund's adjuvant）引起的机械性痛觉过敏。BI-113823可用于研究慢性炎症性疼痛。

AS2795440 是一种 PIKfyve 抑制剂。它能够选择性地抑制促炎细胞因子（如 IL-12p40 和 IL-6）的产生以及 B 细胞的活化，而不影响 Ca2+ 信号传导。AS2795440 显示出可以显著减轻佐剂性关节炎 (AIA) 小鼠模型中的关节炎症和骨质流失的效果。AS2795440 可用于炎症和自身免疫性疾病的研究，如类风湿性关节炎、牛皮癣和炎症性肠病。

AHR-10037是一种非甾体抗炎药，具有镇痛和解热特性以及高治疗指数，低胃毒性，它在抑制急性（伊文思蓝卡拉胶胸腔积液）和慢性（佐剂诱导的关节炎）炎症方面与吲哚美辛相当。研究表明，它在体内转化为环氧合酶抑制剂的前药。

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)

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg/ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g/animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

JC-171 is a selective NLRP3 inflammasome inhibitor, with an IC50 of 8.45 μM for inhibiting LPS/ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages[1]. JC-171 (0-100 μM) blocks NLRP3 inflammasome activation and IL-1β production in primary macrophages dose dependently[1]. Cell Viability Assay[1] Cell Line: J774A.1 murine macrophage cells JC-171 treatment delays the progression and reduces the severity of experimental autoimmune encephalomyelitis (EAE) in mouse[1]. Animal Model: Mice immunized subcutaneously with 200 μg Myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide emulsified in Complete Freund's Adjuvant (CFA) on day 0 followed by injection of 200 ng of pertussis toxin. [1]. Chunqing Guo, et al. Development and Characterization of a Hydroxyl-Sulfonamide Analogue, 5-Chloro-N-[2-(4-hydroxysulfamoyl-phenyl)-ethyl]-2-methoxy-benzamide, as a Novel NLRP3 Inflammasome Inhibitor for Potential Treatment of Multiple Sclerosis. ACS Chem Neurosci. 2017 Oct 18;8(10):2194-2201.

Cryogenine is an alkaloid originally isolated from H. salicifolia that has anti-inflammatory activity.1 It inhibits prostaglandin synthetase (IC50 = 424 μM). Cryogenine (100 mg/kg per day, p.o.) reduces paw edema and the mean arthritic index in a rat model of adjuvant-induced polyarthritis.2 |1. Lema, W.J., Blankenship, J.W., and Malone, M.H. Prostaglandin synthetase inhibition by alkaloids of Heimia salicifolia. J. Ethnopharmacol. 15(2), 161-167 (1986).|2. Kosersky, D.S., Brown, J.K., and Malone, M.H. Effects of cryogenine on adjuvant-induced arthritis and serum turbidity in rats. J. Pharm. Sci. 62(12), 1965-1971 (1973).

Taraxasteryl acetate 是分离自矢状疟原虫中，具有广谱的抗炎活性。它能够改善右旋糖酐、酵母聚糖及花生四烯酸诱导的大鼠后爪水肿。它可用于研究局部炎症。

Baicalein monohydrate is an inhibitor of 12-lipoxygenase, leukotriene biosynthesis and release of lysosomal enzymes. It also inhibits cellular Ca2+ uptake and mobilization and adjuvant-induced arthritis.

R-130823 is a ighly selective inhibition against mitogen-activated protein kinase p38alpha (IC50=22 nM). The release of tumor necrosis factor-alpha, interleukin-1beta, -6 and -8 was inhibited in lipopolysaccharide-stimulated human blood pretreated by R-130823 , with IC50 values of 0.089, 0.066, 0.95 and 0.16 microM, respectively. R-130823 reduced the established hind paw swelling in rat adjuvant-induced arthritis, while methotrexate showed no suppression. In the same model, R-130823 ameliorated adjuvant-induced hyperalgesia with rapid onset and long duration comparable to a cyclooxygenase-2 inhibitor, celecoxib.

Flavokawain B (Flavokavain B) 是从卡瓦醉椒的根提取物中，分离出的查尔酮。它是一种凋亡诱导剂，可抑制各种癌细胞株生长。它以极低的无毒浓度抑制人脑内皮细胞的迁移和血管形成，具有抗血管生成活性。

MF-592 is a potent and selective antagonists of the EP4 receptor. MF-592 demonstrated good functional potency (hEP4 IC50 = 3 nM) and potent inhibition of PGE2 modulated TNFa release in LPS stimulated human whole blood (hWB) (IC50 = 78nM). In addition, it showed an excellent oral pharmacokinetic (PK) profile and in vivo efficacy in a rat chronic adjuvant-induced-arthritis model (ED50 = 0.1 mg/kg/day).. MF-592 has a desirable overall preclinical profile that suggests it is suitable for further development.

D-Mannuronic acid sodium，一种可从Macrocystis pyrifera中分离得到的化合物，显示出在自身免疫性脑脊髓炎(EAE)、佐剂性关节炎(AIA)、肾病综合征以及急性肾小球肾炎的研究中具有潜在应用价值。

I-287为一种口服活性PAR2选择性抑制剂，能对Gαq和Gα12/13的活性以及其下游效应物施加负异构调控。该化合物能够减轻Complete Freund's adjuvant引发的小鼠炎症，适用于免疫炎症研究。

K 41498 是一种针对皮质酮释放因子受体2α（CRF2α）和CRF2β的肽拮抗剂，其在表达人类受体的HEK293细胞中的Ki值分别为0.66和0.62 nM。它对CRF2α和CRF2β具有选择性，与CRF1相比（在表达人类受体的HEK293细胞中Ki值为425 nM）。K 41498 (1.84 µg/动物, 静脉注射) 能够阻止大鼠由于尿催肾上腺皮质激素引发的低血压。通过脊髓内给药，K 41498 (0.075-0.5 µmol/动物) 能降低完全弗氏佐剂引起的大鼠模型中机械性爪撤回阈值。

PVP-037.2,一种TLR7/8激动剂,能够作为疫苗的辅助佐剂,有效促进TH1型免疫反应并提升抗原特异性抗体IgG1与IgG2c的生成.