RECENT ADVANCES IN INDAZOLE-BASED DERIVATIVES OF VEGFR-2 KINASE INHIBITORS AS AN ANTI-CANCER AGENT

Abstract

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. Cancer continues increasing a serious threat to a people health. Cancer is the uncontrolled growth of abnormal cells in the body; cancer develops when the body’s normal control mechanism stops working. Many anti-cancer agents have been developed in recent year but survival rate does not satisfy. Therefore, through many efforts to develop novel anti-cancer agents to cover up for deficiency. Indazole is class of heterocyclic bioactive compounds, making structural modification on active indazole derivatives giving a variety of biological activities such as anti-depressant and antitumor anti-bacterial, anti-inflammatory, anti- hypertensive. These study through various literature focus on recent research of indazole derivatives as an anti-cancer will be useful for further development of Indazole base derivatives with new scaffold and high potency as anti-cancer agent. Recently many efforts have been taken for the development of indazole derivatives as vascular endothelial growth factor-2 (VEGFR-2) kinase inhibitors give good anti-tumor activities. Vascular endothelial growth factor-2 plays a role in tumor angiogenesis. Newly synthesized 2-(4-(1H-indazol-6-yl)-1H-pyrazol-1-yl) acetamide derivatives were designed as VEGFR-2 inhibitors based on scaffold hopping strategy. These compounds exhibited the excellent inhibitory in both vegfr-2 and tumor cells proliferation.  A novel vegfr2 inhibitor CHMFL-VEGFR2-002 showed high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R etc.  CHMFL-VEGFR2-002 given potent inhibitory activity against VEGFR2 kinase.  CHMFL-VEGRF2-002 as a research tool for developing new function of VEGFR2 kinase as well as a potential antiangiogenetic agent for the cancer therapy.