Vascular endothelial growth factor receptor (VEGFR-2)/KDR inhibitors: Medicinal chemistry perspective

Abstract New blood vessels formation from the existing vasculature is called angiogenesis. It is an essential physiological process for the growth of cells, tissue repair, wound healing, and reproductive system of females. The process of angiogenesis regulation is related to diseases such as rheumatism arthritis, diabetes, atherosclerosis, and cancer. The growth and metastasis of the tumor directly depend on the process of tumor angiogenesis. Tumor angiogenesis is regulated by the proangiogenic factors and anti-angiogenic factors formed by the host cells as well as the tumor cells. Different growth factors, namely VEGF, PDGF, FGF, and cytokines, have a key impact on the process of angiogenesis. Amongst various growth factors, vascular endothelial growth factors (VEGF) and VEGFR-2 (KDR); exhibits a significant impact on the process of angiogenesis. After the activation initiated, KDR undergoes autophosphorylation that ultimately leads to a proliferation of the endothelial cells, tumor angiogenesis, tumor growth, and metastasis. VEGFR-2 overexpression is observed in different kinds of cancer, namely breast cancer, cervical cancer, non-small cell lung cancer, hepatocellular carcinoma, renal carcinoma, and likewise. Over the past decade, several VEGFR-2 inhibitors have been developed. Angiogenesis inhibition by blocking the VEGFR-2 is an emerging strategy to develop selective and specific anticancer agents. The review articles published before were based on the structure and biology of VEGFR-2 rather than medicinal chemistry. While the emphasis of the current review is to summarise, the recent advancement regarding VEGFR-2 inhibitors concerning medicinal chemistry approaches.