chemokine a 3

AMG 487 是可口服的选择性趋化因子受体3拮抗剂，对 I-IP-10、I-ITAC 和 MIG 的 IC50 值分别为 8、15 和 36nM。

CCR7 Ligand 1 (CCR7-Cmp2105) is an allosteric Ligand and antagonist for human CC chemokine receptor 7 (CCR7) with a Kd of 3 nM. CCR7 Ligand 1, thiadiazole-dioxide ligan, suppresses arrestin binding in response to activation by CCL19 with an IC50 of 7.3 μM

CRTh2 antagonist 3 is a powerful chemokine receptor homologous molecule expressed on Th2 cell (CRTh2) antagonists. CRTh2 antagonist 3 enhanced the activity of PDK1 on short peptide substrates with EC50 of 2 μM and Kd of 8.4 μM. CRTh2 antagonist 3 has the

GW 766994 is a specific and oral chemokine receptor-3 (CCR3) antagonist. It has the potential for asthma and eosinophilic bronchitis treatment.

AZD2423 is a potent, selective, orally bioavailable, and non-competitive CCR2 chemokine receptor negative allosteric modulator and it has an IC50 of 1.2 nM for CCR2 Ca2+ flux [1][2][3].

Burixafor（又名TG-0054）是一种口服可用的CXC趋化因子受体4（CXCR4）抑制剂，具有受体结合和造血干细胞动员活性。Burixafor通过结合到CXCR4化趋受体，阻止基质衍生因子-1（SDF-1或CXCL12）与CXCR4受体的结合及其随后的受体激活，从而可能实现造血干细胞和祖细胞从骨髓释放到血液中的动员。备注：元素分析显示该化合物是含有3个HBr和3个水的盐。

YM-355179 is a novel, selective antagonist of CC chemokine receptor 3 with oral activity.

(±)14(15)-EET is a metabolite of arachidonic acid that is formed via epoxidation of arachidonic acid by cytochrome P450.[1],[2] It prevents increases in leukotriene B4, ICAM-1, and chemokine (C-C motif) ligand 1 (CCL2) induced by oxidized LDL in primary rat pulmonary artery endothelial cells (RPAECs) when used at a concentration of 1 μM.[3] (±)14(15)-EET induces dilation of preconstricted isolated canine coronary arterioles (EC50 = 0.2 pM).[4] It reduces myocardial infarct size as a percentage of the area at risk in a canine model of ischemia-reperfusion injury induced by left anterior descending coronary artery (LAD) occlusion when administered at a dose of 0.128 mg kg prior to occlusion or reperfusion.[5] Reference：[1]. Chacos, N., Falck, J.R., Wixtrom, C., et al. Novel epoxides formed during the liver cytochrome P-450 oxidation of arachidonic acid. Biochem. Biophys. Res. Commun. 104(3), 916-922 (1982).[2]. Oliw, E.H., Guengerich, F.P., and Oates, J.A. Oxygenation of arachidonic acid by hepatic monooxygenases. Isolation and metabolism of four epoxide intermediates. J. Biol. Chem. 257(7), 3771-3781 (1982).[3]. Jiang, J.-X., Zhang, S.-J., Xiong, Y.-K., et al. EETs attenuate ox-LDL-induced LTB4 production and activity by inhibiting p38 MAPK phosphorylation and 5-LO BLT1 receptor expression in rat pulmonary arterial endothelial cells. PLoS One 10(6), e0128278 (2015).[4]. Oltman, C.L., Weintraub, N.L., VanRollins, M., et al. Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation. Circ. Res. 83(9), 932-939 (1998).[5]. Nithipatikom, K., Moore, J.M., Isbell, M.A., et al. Epoxyeicosatrienoic acids in cardioprotection: Ischemic versus reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 291(2), H537-H542 (2006).

Emestrin is a mycotoxin originally isolated from E. striata that has antimicrobial, immunomodulatory, and cytotoxic activities.1,2,3,4,5 It is active against the fungi C. albicans and C. neoformans, as well as the bacteria E. coli, S. aureus, and methicillin-resistant S. aureus (MRSA; IC50s = 3.94, 0.6, 2.21, 4.55, and 2.21 μg ml, respectively).2 Emestrin is a chemokine (C-C motif) receptor 2 (CCR2) antagonist (IC50 = 5.4 μM in a radioligand binding assay using isolated human monocytes).3 Emestrin (0.1 μg ml) induces apoptosis in HL-60 cells.4 It induces heart, thymus, and liver tissue necrosis in mice when administered at doses ranging from 18 to 30 mg kg.5 |1. Seya, H., Nakajima, S., Kawai, K.-i., et al. Structure and absolute configuration of emestrin, a new macrocyclic epidithiodioxopiperazine from Emericella striata. J. Chem. Soc. Chem. Commun. 10, 657-658 (1985).|2. Herath, H.M.T.B., Jacob, M., Wilson, A.D., et al. New secondary metabolites from bioactive extracts of the fungus Armillaria tabescens. Nat. Prod. Res. 27(17), 1562-1568 (2013).|3. Herath, K.B., Jayasuriya, H., Ondeyka, J.G., et al. Isolation and structures of novel fungal metabolites as chemokine receptor (CCR2) antagonists. J. Antibiot. (Tokyo) 58(11), 686-694 (2005).|4. Ueno, Y., Umemori, K., Niimi, E.-c., et al. Induction of apoptosis by T-2 toxin and other natural toxins in HL-60 human promyelotic leukemia cells. Nat. Toxins 3(3), 129-137 (1995).|5. Terao, K., Ito, E., Kawai, K.-i., et al. Experimental acute poisoning in mice induced by emestrin, a new mycotoxin isolated from Emericella species. Mycopathologia 112(2), 71-79 (1990).

CAY10748 is an agonist of stimulator of interferon genes (STING; IC50= 0.3794 μM in a competition binding assay).1It activates STING in STING-expressing, but not STING knockout, THP-1 cells (EC50s = 0.287 and >100 μM, respectively, in a reporter assay). It induces phosphorylation of STING at the serine in position 366, as well as phosphorylation of TBK1 and IFN regulatory factor 3 (IRF3), indicating activation of the STING-TBK1-IRF3 signaling pathway. CAY10748 increases the secretion of IFN-β and the levels of chemokine (C-X-C motif) ligand 10 (CXCL10), and IL-6 in peripheral blood mononuclear cells (PBMCs) when used at a concentration of 10 μM. It also reduces tumor growth in a CT26 murine colon cancer model when administered at a dose of 0.15, but not 1.5, mg/kg. 1.Xi, Q., Wang, M., Jia, W., et al.Design, synthesis, and biological evaluation of amidobenzimidazole derivatives as stimulator of interferon genes (STING) receptor agonistsJ. Med. Chem.63(1)260-282(2019)

CXCR2-IN-2 is a selective, brain penetrant, and orally bioavailable CXCR2 antagonist (IC50=5.2 nM 1 nM in β-arrestin assay CXCR2 Tango assay, respectively). CXCR2-IN-2 displays ~730-fold selectivity over CXCR1 and >1900-fold selectivity over all other chemokine receptors. CXCR2-IN-2 inhibits human whole blood Gro-α induced CD11b expression with an IC50 of 0.04 μM[1]. CXCR2-IN-2 (compound 68) (1-10 mg kg; p.o.; twice daily for 3 days) dose-dependently reduces neutrophil infiltration in vivo in rat and mouse air pouch models[1]. [1]. Lu H, et al. Discovery of Novel 1-Cyclopentenyl-3-phenylureas as Selective, Brain Penetrant, and Orally Bioavailable CXCR2 Antagonists. J Med Chem. 2018;61(6):2518-2532.

CXCR3 antagonist 6c is an antagonist of chemokine (C-X-C motif) receptor 3 (CXCR3).1It inhibits calcium mobilization induced by chemokine (C-X-C motif) ligand 11 (CXCL11) in HEK293 cells expressing the human receptor (IC50= 0.06 μM). It is selective for CXCR3 over a panel of 14 human G protein-coupled receptors at 10 μM. CXCR3 antagonist 6c inhibits CXCR3-mediated migration of isolated human T cells (IC50= ~100 nM). 1.Cole, A.G., Stroke, I.L., Brescia, M.-R., et al.Identification and initial evaluation of 4-N-aryl-[1,4]diazepane ureas as potent CXCR3 antagonistsBioorg. Med. Chem. Lett.16(1)200-203(2006)

Resolvin D2 n-3 DPA (RvD2 n-3 DPA) is a specialized pro-resolving mediator (SPM).1It is formed from docosapentaenoic acid , an intermediate in the conversion of eicosapentaenoic acid to docosahexaenoic acid , in human leukocytes. RvD2 n-3 DPA (1 nM) reduces TNF-α-induced chemotaxis and adhesion of isolated human neutrophils.In vivo, RvD2 n-3 DPA (100 ng animal; i.v.) reduces peritoneal neutrophil infiltration and exudate levels of IL-6 and chemokine (C-C motif) ligand 2 (CCL2) in a mouse model of zymosan-induced inflammation. 1.Dalli, J., Colas, R.A., and Serhan, C.N.Novel n-3 immunoresolvents: Structures and actionsSci. Rep.31940(2013)

Interleukin-2-inducible T cell kinase (ITK) is a non-receptor tyrosine kinase expressed in T cells, NKT cells and mast cells which plays a crucial role in regulating the T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR-mediated signaling pathways. ITK inhibitors can be used for the treatment of inflammation and immune-mediated disorders. ITK inhibitor (N-[5-[[3-[(4-Acetylpiperazin-1-yl)carbonyl]-4-methyl-6-methoxy-phenyl]thio]thiazol-2-yl]-4-(N-1,2-dimethylpropylaminomethyl)benzamide) is the analogue of BMS-509744, which can potently and selectively inhibit Itk kinase activity. In vitro: BMS-509744 could reduce TCR-induced functions including PLCγ1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion, and T-cell proliferation in vitro in both human and mouse cells [1]. In vivo: BMS-509744 suppressed the production of IL-2 induced by anti-TCR antibody administered to mice. BMS-509744 also significantly diminishes lung inflammation in a mouse model of ovalbumin-induced allergy/asthma [1]. Clinical trial: Up to now, both BMS-509744 and ITK inhibitor is still in the preclinical development stage.

Resolvin D5是一种从DHA中提取的氧化脂质介质，具有抗炎作用，在LPS刺激的THP-1细胞中通过ERK-NF-κB信号通路抑制IL-6和CCL5的产生。

SB297006 是一种CCR3拮抗剂，IC50为39 nM。它能够显著抑制 CCL11 处理的神经祖细胞的增殖和神经球形成。

CCR4 antagonist 3-1 是一种具有较低活性的趋化因子受体 4 (CCR4) 拮抗剂，对 [125I]TARC (胸腺和活化调节趋化因子) 具有抑制作用，IC50 值为 1.7 μM。CCR4 antagonist 3-1 对放射标记的[125I]TARC和巨噬细胞来源的趋化因子(MDC) 与 CEM 细胞表面的CCR4 受体的结合有抑制作用， 并对 TARC 介导的 CEM 细胞的体外迁移有抑制作用，IC50 值为 6.4 μM。

CXCR2 antagonist 3 (compound 11h) is a highly effective antagonist of CXC chemokine receptor 2 (CXCR2). It displays potent activity in inhibiting neutrophil infiltration into the air pouch, with double-digit nanomolar potencies against CXCR2. Moreover, CXCR2 antagonist 3 reduces the infiltration of neutrophils and MDSCs, while enhancing the infiltration of CD3+ T lymphocytes into Pan02 tumor tissues [1].

BAY-3153 是一种选择性的 CCR1(C-C motifchemokine receptor1) 拮抗剂 (humanIC50=3 nM ; ratIC50=11 nM ; miceIC50=81 nM)。

Chemerin-9 (149-157) TFA 作为趋化因子样受体1 (CMKLR1) 的有效激动剂，展现出抗炎活性，并能促进Akt与ERK磷酸化及活性氧生成，进而改善Aβ1-42诱发的记忆障碍。此外，该化合物还参与调节免疫反应、脂肪细胞分化以及糖代谢。

CTCE-0214 是一种 CXCR4(chemokine CXC receptor 4) 激动剂，是 SDF-1α 肽类似物。CTCE-0214 具有抗炎活性，可用于炎症败血症和系统性炎症综合征的研究。

STAT6-IN-2（R）-84 是一种 STAT6 抑制剂，抑制 eotaxin-3 的分泌，抑制 293-EBNA 细胞中诱导 STAT6 报告荧光素酶活性，抑制 STAT6 的酪氨酸磷酸化。

LIH383是一种趋化因子(C-X-C motif) 受体7 (CXCR7)的多肽激动剂，属于趋化因子和阿片肽清除受体。它专一性激活CXCR7 (EC50 = 0.61 nM)，在3 µM浓度时，相比μ-、δ-、κ-阿片受体以及诺氨酸阿片肽（NOP）受体的β-arrestin招募实验中表现出高选择性。LIH383（3 µM）通过阻止U87-ACKR3细胞中，由非选择性阿片受体激动剂dynorphin A诱导的CXCR7对阿片肽的摄取，发挥作用。

EP4 antagonist 14是一种前列腺素E2（PGE2）受体亚型EP4的拮抗剂，其在使用表达人源受体的HEK293细胞的报告基因测定中的IC50值为1.1 nM。它还能抑制PGE2诱导的同种细胞中的β-阿雷斯汀招募（IC50 = 0.9 nM）。EP4 antagonist 14（10 µM）能减少RAW 264.7巨噬细胞中PGE2诱导的mRNA表达，这些mRNA编码Il-4、巨噬细胞甘露糖受体1（Mrc1）、几丁质酶样蛋白3（Chil3）、趋化因子（C-X-C）基序配体1（Cxcl1）、表达在髓样细胞上的触发受体2（Trem2）和精氨酸酶-1（Arg1）。在体内，EP4 antagonist 14（每天30 mg/kg），结合抗PD-1抗体，能够在CT26小鼠结肠癌模型中抑制肿瘤生长并增加CD8+ T细胞对肿瘤的浸润。