AMG 487

"目录号: HY-15319 ee.: 99.97%

GPCR/G ProteinImmunology/Inflammation-

AMG 487 是一种有效的趋化因子受体CXCR3拮抗剂，能够抑制125I-IP-10 和125I-ITAC 与 CXCR3 结合，IC50值分别为 8.0 和 8.2 nM。

CXCR

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生物活性

Description

AMG 487 is an antagonist of the chemokine receptorCXCR3, which inhibits binding of125I-IP-10 and125I-ITAC to CXCR3 withIC50values of 8.0 and 8.2 nM, respectively.

IC50& Target

IC50: 8.0 nM (125I-IP-10 binding to CXCR3), 8.2 nM (125I-ITAC binding to CXCR3)

In Vitro

AMG 487 inhibits CXCR3-mediated cell migration by the three CXCR3 chemokines (IP-10 IC50=8 nM, ITAC IC50=15 nM, and MIG IC50=36 nM). Furthermore, AMG 487 inhibits calcium mobilization in response to ITAC (IC50=5 nM)[1]. AMG487 (1 μM) develops into fewer lung metastases, and the lungs are significantly smaller than vehicle-treated lungs[2]. AMG487 abrogates proliferation/survival of C26 tumour cells[3].

In Vivo

AMG 487 (0.03-10 mg/kg, s.c.) exhibits significant reduction in cellular infiltration into the lungs in a dose dependent manner[1]. AMG487 (5 mg/kg, s.c., twice daily) develops fewer metastases than that in vehicle-treated mice[2]. AMG487 (5?mg/kg, s.c.)-treated mice exhibits fewer pulmonary nodules than the control mice in both the models. AMG487 reduces the tumour volume[3].

References

[1].Johnson M, 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, 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].Cambien B, et al. Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009 Jun 2;100(11):1755-64.

[4].Henne KR, et al. Sequential metabolism of AMG 487, a novel CXCR3 antagonist, results in formation of quinone reactive metabolites that covalently modify CYP3A4 Cys239 and cause time-dependent inhibition of the enzyme. Drug Metab Dispos. 2012 Jul;40(7):142