ML-221

An APJ receptor antagonist (IC50 = 4.8 µM); selective for APJ over AT1 (IC50 = >78 µM); antagonizes apelin 13-induced activation of APJ in cAMP and β-arrestin recruitment assays (IC50s = 0.7 and 1.75 µM, respectively); inhibits proliferation and angiogenesis in Mz-ChA-1 cholangiocarcinoma cells from 5-15 µM; reduces tumor growth in a Mz-ChA-1 mouse xenograft model at 150 µg/kg; reduces sciatic CCI-induced mechanical allodynia and heat hyperalgesia in rats at 10 µg/animal; inhibits pathological angiogenesis and enhances normal vessel recovery in retinal ischemic regions in a mouse model of oxygen-induced retinopathy