AMG-487 is a potent and selective orally bioavailable chemokine (C-X-C motif) receptor 3 (CXCR3) antagonist that displays dose- and time-dependent pharmacokinetics in human subjects after multiple oral dosing. AMG-487 is an 8-azaquinazolinone, it can prevent the chemokines I-IP-10 and I-ITAC from binding to CXCR3. The preclinical properties of AMG487 has been extensively studied. The compound displays a greater than 1000-fold selectivity for CXCR3 versus a panel of other receptors, including 11 chemokine receptors. The safety profile of AMG487, as assessed by various genotoxicity and cardiotoxicity assays, revealed no major concerns. The ability of AMG487 to inhibit inflammatory cell migration in vivo was confirmed in a mouse model of bleomycin-induced cellular recruitment, where AMG487 significantly reduced infiltration of macrophages and lymphocytes into the lungs in CXCR3-KO mice. In a mouse model for idiopathic pneumonia syndrome (IPS), AMG487 reduced recruitment of donor T cells to the lung after allogeneic stem cell transplantation, leading to improved survival rates. Likewise, reductions in inflammation, pannus formation, and cartilage damage were observed upon administering AMG487. The preclinical studies convincingly paved the way for clinical studies on two inflammation-related diseases: psoriasis and rheumatoid arthritis. In 2003, results of a Phase I trial on AMG487 were disclosed. The compound was assessed for safety and pharmacokinetics in 30 healthy males in a randomised, double blind, placebo-controlled dose-escalation study. Generally, the compound was well tolerated and adverse events were mild to moderate. Disappointingly, no significant differences in the endpoints (psoriasis severity index or physician global assessment scores) were seen between patient groups. AMG-487 progressed to Phase II clinical trials but has been withdrawn because of lack of efficacy.