AMG 487

AMG 487 is an orally active and selective antagonist of CXC chemokine receptor 3 (CXCR3) which inhibits the binding of CXCL10 and CXCL11 to CXCR3 with IC₅₀s of 8.0 and 8.2 nM, respectively^[1]. 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].