AMG 487

产品说明书

Print
Chemical Structure| 473719-41-4 同义名 : -
CAS号 : 473719-41-4
货号 : A427101
分子式 : C32H28F3N5O4
纯度 : 99%+
分子量 : 603.59
MDL号 : MFCD11111772
存储条件：

Pure form Keep in dark place, sealed in dry, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 CXC chemokine receptor-3 (CXCR3) is a G-protein coupled receptor (GPCR) predominantly expressed on activated T lymphocytes that promote Th1 responses[3]. AMG 487 is the targeted blocker of chemokine receptor CXCR3 and improves inflammatory symptoms by blocking the inflammatory cycle[4]. AMG487 treatment in collagen-induced arthritis(CIA) mice decreased mRNA and protein expression levels of CXCR3, IL-17A, RORγt, and STAT3. Therefore, it can be concluded that the anti-arthritic effect of AMG487 is caused by the inhibitory action on IL-17A and by downregulating RORγt/STAT3 expression in CIA the model[5]. Pharmacological blockade of CXCR3 using local injection of its inhibitor, AMG487, into the anterior cingulate cortex (ACC) significantly attenuated hyperalgesia induced by chronic constriction injury and suppressed the phosphorylation of extracellular signal-regulated kinase (ERK)[6]. AMG487 application might alleviate PDGFR-β and occludin loss, and decreased the residual content of retinal albumin in the streptozocin-induced DR mouse model via the inhibition of oxidative and endoplasmic reticulum stress, in which p38 activation was also involved[7]. AMG487 significantly alleviated joint inflammation by decreasing GITR+CD25+, GITR+CD45+, GITR+IL-9+, GITR+NF-κB+ CD45+CD4+, CD45+CCR6+, CD45+IL-6+ cells, CD45+IL-17A+, and CD45+IL-21+, and increasing GITR+Foxp3+ and GITR+STAT6+ cells[8].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.66mL

0.33mL

0.17mL

8.28mL

1.66mL

0.83mL

16.57mL

3.31mL

1.66mL
参考文献

[1]Johnson M, Li AR, et al. Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3. Bioorg Med Chem Lett. 2007 Jun 15;17(12):3339-43.

[2]Walser TC, Rifat S, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res. 2006 Aug 1;66(15):7701-7.

[3] Stefania Storelli,et al. Synthesis and structure-activity relationships of 3H-quinazolin-4-ones and 3H-pyrido[2,3-d]pyrimidin-4-ones as CXCR3 receptor antagonists. Arch Pharm (Weinheim). 2007 Jun;340(6):281-91.

[4]Chenchen Qin,et al. In Vitro Immunological Effects of CXCR3 Inhibitor AMG487 on Dendritic Cells. Arch Immunol Ther Exp (Warsz). 2020 Apr 1;68(2):11.

[5]Saleh A Bakheet,et al. CXCR3 antagonist AMG487 suppresses rheumatoid arthritis pathogenesis and progression by shifting the Th17/Treg cell balance. Cell Signal. 2019 Dec;64:109395.

[6]Jing Qin,et al.CXCR3 contributes to neuropathic pain via ERK activation in the anterior cingulate cortex. Biochem Biophys Res Commun. 2020 Oct 15;531(2):166-171.

[7]Honggang Wang,et al. Blocking CXCR3 with AMG487 ameliorates the blood-retinal barrier disruption in diabetic mice through anti-oxidative. Life Sci. 2019 Jul 1;228:198-207.

[8]Saleh A Bakheet,et al. CXCR3 antagonist AMG487 inhibits glucocorticoid-induced tumor necrosis factor-receptor-related protein and inflammatory mediators in CD45 expressing cells in collagen-induced arthritis mouse model. Int Immunopharmacol. 2020 Jul;84:106494.