Tumor angiogenesis has always been a major gap for effective cancer therapy. Interruption
of aberrant angiogenesis by specific inhibitors targeting receptor tyrosine kinases
(RTKs) has been of great interests to medicinal chemists. Among the factors that are involved
in tumor angiogenesis, vascular endothelial growth factor receptor-2 (VEGFR-2) is validated as the
most closely related factor which can drive angiogenesis through binding with its natural ligand VEGF. The
well-validated VEGF-driven VEGFR-2 signaling pathway can stimulate many endothelial responses, including
increasing vessel permeability and enhancing endothelial cell proliferation, migration and differentiation.
Consequently, circumventing angiogenesis by VEGFR-2 inhibitors represents a promising strategy for counteracting
various VEGFR-2-mediated disorders as well as drug resistance. Over the past decades, a considerable
number of novel small molecular VEGFR-2 inhibitors have been exploited with diverse chemical scaffolds.
Especially, recent frequently launched inhibitors have declared their research values and therapeutic potentials
in oncology. Still, the antiangiogenesis based treatment remains an ongoing challenge. In this review,
a comprehensive retrospective of newly emerged VEGFR-2 inhibitors have been summarized, with the emphasis
on the structure-activity relationship (SAR) investigation, and also binding patterns of representative
inhibitors with biotargets. On the basis of all of this information, varied strategies for developing potent
VEGFR-2 inhibitors and the future prospect of the clinical application of antiangiogenic inhibitors are discussed