chemokines

CCR2 antagonist 4 (Teijin compound 1) 是高效的、特异性的CCR2拮抗剂，对 CCR2b 的IC50为 180 nM，抑制 MCP-1 诱导的趋化作用的 IC50为 24 nM。

3-Hydroxykynurenamine, also known as 3-Hydroxy-L-kynurenamine or 3-HKA, is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1 NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction.This compound is unstable in powder form and other related salt forms are recommended.

Valencene (NSC-148969) 是一种从 Cyperus rotundus 中分离出来的倍半萜类化合物，是柑橘类水果和柑橘类衍生气味的香气成分。ValenceneValencene 具有抗过敏、抗炎、抗黑色素生成、和抗氧化活性。通过阻断 NF-κB 通路，Valencene 通过阻断 NF-κB 通路抑制 Th2 趋化因子和促炎性趋化因子的过度表达。

KS370G (Caffeic Acid Phenethyl Amide) 抑制 UUO 诱导的肾纤维化标志物表达。KS370G 是一种具有口服活性的降糖和心血管保护剂，可减少梗阻肾脏中胶原蛋白的沉积，并显著降低肾脏炎症趋化因子 粘附分子和单核细胞标志物的表达，改善压力过载小鼠心脏左室肥厚和功能。KS370G 可用于研究肾阻塞性肾病。

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8 9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26 DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630 624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20 2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

BRD5075是GPR65的高效激活剂,能促进依赖GPR65的cAMP生成.此外,它还能抑制IL-1、IL-2、TNF以及趋化因子的基因表达,展示了其在多发性硬化症与炎症性肠病(IBD)研究中的应用潜力.

AMG 487 is an effective and selective antagonist of chemokine receptor 3. AMG 487 inhibited CXCR3-mediated cell migration induced by three CXCR3 chemokines, IP-10, ITAC and MIG (IC50: 8, 15 and 36 nM, respectively).

GA-O-02，一种18β-Glycyrrhetinic acid衍生物，具有显著的抗菌和抗炎效果。该化合物通过抑制NO、促炎细胞因子及趋化因子来发挥其抗炎作用，并对革兰氏阳性菌显示出高度的抗菌活性。

Lintuzumab (HuM-195) 是一种针对细胞表面骨髓单核细胞分化抗原 CD33 的非偶联人源化小鼠单克隆抗体，具有抗白血病活性，可减少 AML 细胞产生 TNFα 诱导的促炎细胞因子和趋化因子。Lintuzumab 具有抗肿瘤活性，通过 CDC 或者 ADCC 直接诱导细胞死亡。

PB118是一种新型组蛋白去乙酰化酶 6（HDAC6）抑制剂，具备穿越血脑屏障的能力，可用于AD治疗。PB118 对 HDAC6 的 IC50 为 5.6 nM。

Ergosta-7,22-dien-3-one 是一种羊毛甾烷，能够从台湾灵芝的子实体中分离得到。Ergosta-7,22-dien-3-one 具有促炎特性，它能刺激一氧化氮的产生，诱导基因的表达，并诱导 J774A.1 细胞产生 TLRs、细胞因子、趋化因子和细胞粘附分子。

Murabutide是一种合成的安全免疫调节剂，能够降低CD4和CCR5受体的表达，并促使β-趋化因子的高水平分泌，从而增强机体对病毒感染的非特异性防御能力。此外，Murabutide不会干扰病毒的进入过程、逆转录酶的活性或是在感染细胞的细胞质中早期前病毒DNA的形成。

Antileukinate is a synthetic hexapeptide with an acetylated amino terminus and an amidated carboxyl terminus that inhibits the binding of CXC chemokines to the chemokine receptor CXCR2. It inhibits IL-8 binding to neutrophils (Ki = 2.7-13 μM), prevents neutrophil chemotaxis and β-glucuronidase release, and blocks IL-8-induced skin edema in rabbits. At 53 mg/kg, antileukinate has been shown to protect mice against acute pancreatitis and associated lung injury.

TMC353121 是呼吸道合胞病毒 (RSV) 融合抑制剂，具有抗 RSV 活性，抑制炎性细胞因子 TNF-α、IL-6 和 IL-1β 以及趋化因子、KC、IP-10、MCP 和 MIP1-α 的产生。

Zharp1-211是一种选择性和有效的RIPK3抑制剂，显著降低IECs中JAK stat1介导的趋化因子和MHC II类分子的表达，恢复肠道稳态，并抑制移植物抗宿主病（GVHD），用于胃肠道炎症。

IMMH001, also known as SYL930, is an orally active compound that exhibits potent selectivity as an agonist for the S1P1 receptor, which is the sphingosine-1-phosphate receptor 1. This compound effectively reduces the levels of various chemokines and proinflammatory cytokines, such as IL-1β, IL-5, IL-18, IP10, CCL3, and CCL5. IMMH001 finds utility in research focused on rheumatoid arthritis (RA) [1] [2].

DPP-4-IN-8 (compound 27) 是一种高效的选择性DPP4抑制剂，具有 0.96 μM 的 Ki。该化合物能够抑制 Caco-2 和 HepG-2 细胞中的 DPP4 二肽酶活性，并剂量依赖性地降低 TNF-α、IL-6 和 IL-1β 的表达水平[1]。

SHP2-IN-35 (Compound 3f) 是一种SHP2抑制剂，在癌细胞 RKO、SW480 和 CT26 中表现出抗增殖活性，IC50分别为 5.72 μM、3.71 μM 和 1.42 μM。该化合物抑制PI3K-Akt信号通路，调节细胞周期相关基因的表达，诱导线粒体自噬 (autophagy)，并在肿瘤微环境 (TME) 中抑制某些细胞因子和趋化因子的表达，从而调节肿瘤进展。

Sophocarpine 是一种从传统草药苦参中提取的重要生物碱。苦参具有抗病毒、抗肿瘤和抗炎等多种药理作用。它通过多种机制显著抑制癌细胞的生长，具有抗肿瘤活性。

Lipopolysaccharides, from S. marcescens (Serratia marcescens) 是来源于粘质沙雷氏菌的脂多糖内毒素和TLR-4激活剂，其属于S型LPS，可作为致病相关分子模式 (PAMP) 激活免疫系统，并诱导细胞分泌迁移体。该脂多糖具有三部分的典型结构：O 抗原 (O-antigen)、核心寡糖 (core oligosaccharide) 和脂质 A (Lipid A)。它通过Toll样受体 (TLR4) MD-2在小鼠细胞中诱导NF-κB活化。S. marcescens的Lipopolysaccharides还能够诱导宿主免疫细胞的凋亡，从而抑制宿主的先天免疫。

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。

Myristicin (Myristicine) 是一种在香料和伞形植物中发现的天然产物。肉豆蔻素具有抗胆碱能、抗菌和肝保护作用，还具有抗炎作用，其通过钙途径抑制dsrna 刺激的巨噬细胞中的NO、细胞因子、趋化因子和生长因子。Myristicin 可以诱导细胞凋亡，其特征是改变线粒体膜电位、细胞色素c 释放、Caspase-3激活、parp 切割和DNA 断裂。

K 76 Carboxylic acid effectively blocks human complement from forming tumor cell chemokines.

GA-O-06是一种18β-Glycyrrhetinic acid衍生物，有效的抗菌及抗炎剂。它通过抑制NO、促炎细胞因子以及趋化因子来发挥抗炎效果，并对革兰氏阳性菌展现出高度的抗菌活性。