Definition

Vascular endothelial growth factor receptor (VEGFR) is a receptor protein tyrosine kinase (RPTK) present on the cell surface, distributed in the vascular endothelium, lymphatic vessels and hematopoietic system, including VEGFR-1, VEGFR-2 and VEGFR-3 three subtypes. Downstream signaling pathways are regulated by transducing signals such as VEGF-A, VEGF-B, VEGF-C, and VEGF-D. Among them, VEGFR-2 is responsible for transducing the pro-angiogenic signal in the cardiovascular system, which is considered to be closely related to tumor angiogenesis, and by inhibiting VEGFR-2, it can cut off the downstream pro-angiogenic signal, inhibit tumor angiogenesis, and then cut off the nutrient supply of tumor cells, promote tumor cell death, and play an anti-tumor effect. Therefore, VEGFR-2 is one of the important targets for the discovery of inhibitors related to inhibition of tumor angiogenesis.

VEGFR is a receptor for VEGF. The three types of VEGFR-1 (FLt-1), VEGFR-2 (KDR), and VEGFR-3 form the VEGFR family. VEGFR-1 and VEGFR-2 are mainly expressed in vascular endothelial cells, stimulating endothelial cell proliferation and promoting angiogenesis, and occasionally in tumor cells, VEGFR-3 is expressed transiently in early fetal venous endothelial cells, and is no longer expressed in postnatal and postnatal endothelial cells, and VEGFR-3 in adults is distributed in lymphatic endothelial cells and regulates lymphangiogenesis. VEGFR-2 has been shown to be highly expressed in a variety of malignancies, including ovarian, thyroid, melanoma, and medulloblastoma.

Fig. 1 The molecular structure of VEGF/VEGFR-2. 

Fig. 2 Ligands for different VEGF receptors.

Function

VEGFR-2 binds to a variety of VEGF ligands (VEGF-A, C, D, E) to form homodimeric complexes that alter their protein conformation, autophosphorylate tyrosine residues and conduct signals downstream.

Among them, the main signaling pathways include Ras/Raf/MAPK and PI3K/AKT, which are activated to lead to the activation of transcription factors, interference with cell cycle, promotion of cell migration, maintenance of cell proliferation, inhibition of apoptosis, and promotion of tumorigenesis and development. On the other hand, growing tumor cells can activate HIF-1 α protein in hypoxia, induce VEGF-A transcriptional expression and secretion, bind to VEGFR-2 on vascular endothelial cells surrounding tumor cells, stimulate angiogenesis response, and lead to tumor growth. Therefore, VEGFR-2 signaling can be inhibited by binding to VEGF-A or VEGFR-2 proteins with antibodies, or by inhibiting VEGFR-2 receptor kinase activity by small molecule inhibitors, thereby obtaining therapeutic effects.

In 1971, Dr. Judah Folkman of Harvard University first proposed the theory of tumor angiogenesis, believing that blocking tumor angiogenesis is an effective strategy against tumors. Vascular Endothelial Growth Factor (VEGF) is a signaling protein that stimulates angiogenesis in cells and promotes angiogenesis and regeneration. By binding to the vascular endothelial growth factor receptor (VEGFR, also known as the tyrosine kinase receptor) on the surface of the cell membrane, VEGF produces biological effects through a series of signaling pathways that ultimately lead to angiogenesis.

Fig. 3 VEGF/VEGFR-2 mediated signaling pathways during angiogenesis. 

Mechanism of Action

VEGFR-2 is one of the subtypes of VEGFR, also known as FLK-1, which is found in the endothelium of blood vessels and lymphatic vessels. VEGFR-2 binds to VEGF-C and vegf-D, regulates lymphatic endothelial cells and vascular endothelial cells, promotes the production of lymphatic vessels and blood vessels, and regulates the migration of lymphocytes. VEGFR-2 is closely related to a variety of diseases such as tumors, psoriasis, rheumatoid arthritis, diabetic retinopathy, etc. In particular, it plays a significant role in tumor growth, metastasis and multi-drug resistance of tumors. Therefore, VEGFR-2 has become an ideal target for the treatment of these diseases, especially tumors. At present, inhibition of VEGFR-2 signaling has become one of the most active research areas in anti-tumor research, and a number of VEGFR-2 inhibitors have entered various phases of clinical studies and shown good application progress. Studies have confirmed that vascular endothelial growth factor (VEGF) is overexpressed in a variety of solid tumors, affecting the tumor microenvironment, and is associated with tumor recurrence and metastasis. Among them, VEGFR signaling pathway plays an important role in regulating tumor angiogenesis. The antitumor effects of antiangiogenic drugs have been demonstrated in a variety of tumors. VEGF/VEGFR inhibitors exert important antitumor effects in diseases such as colorectal cancer and gastric cancer.

Alpha Lifetech Inc. is dedicated to developing VEGF receptor 2 diagnostic regents. Alpha Lifetech Inc. is a reputable supplier focusing on research, manufacture and sales of In Vitro Diagnostic (IVD) regents. All the IVD regents offered by Alpha Lifetech Inc. have undergone strict QC validation and are certified by the COA (certificate of analysis). Meanwhile, we can provide customized services according to customers' requirements. Alpha Lifetech Inc. is committed to supplying high-quality, high-sensitivity antigen and antibody products for scientific research and industrial customers. In addition to regular small packages, Alpha Lifetech Inc.'s large-scale fermentation platform also allows us to provide raw material-grade IVD regents for the majority of industrial customers.

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