Angiokinases,such as vascular endothelial-,fibroblast-and platelet-derived growth factor receptors (VEGFRs,FGFRs and PDGFRs) play crucial roles in tumor angiogenesis.Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years.In this study,we presented the design,synthesis,target identification,molecular mechanism,pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152.WXFL-152,identified from a series of 4-oxyquinoline derivatives based on a structure-activity relationship study,inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2,FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro.Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models,including a patientderived tumor xenograft (PDX) model.Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles.In conclusion,WXFL-152,which is currently in phase Ⅰb clinical trials,is a novel and effective tripleangiokinase inhibitor with clear PD and PK in tumor therapy.