Research Bevacizumab Biosimilar CAS:216974-75-3

Bevacizumab Biosimilar is an anti-VEGF monoclonal antibody, which means it is an inhibitor of VEGF. Bevacizumab biosimilar is sold under the brand name Avastin among others. There are also biosimilars of bevacizumab available, such as bevacizumab-awwb, bevacizumab-maly, and bevacizumab-adcd. The synonyms of Bevacizumab are Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF monoclonal antibody, bevacizumab-awwb, rhuMAb-VEGF. Bevacizumab biosimilar Alpha Lifetech Inc. provide is expressed in vitro and it is used for research purpose only.

Figure1: The structure of Bevacizumab

VEGF (Vascular endothelial growth factor), also named VPF (vascular permeability factor), is the main controller of vascular development and blood and lymphatic vessel function in grown-ups. There is a great deal of evidence indicating that vascular endothelial growth factor (VEGF) is important for the survival and proliferation of cancer cells. the VEGF family consists of five structurally correlated factors: VEGF A (also known as VEGF A165, the most well-studied), VEGF B, VEGF C, VEGF D, and placental growth factor (VEGF F). VEGFs play an important role both in health and during illness. In normal physiological states, VEGFs can induce angiogenesis. In abnormal states, VEGFs' expression changes, and they are highly expressed in most malignancies. VEGFs are produced by several types of cells (for example, fibroblasts, inflammatory cells, tumor cells) and typically responds to hypoxia caused by tumor proliferation via the HIF-1a pathway.

VEGF family proteins mainly bind to receptors to exert functions. Cancer cells promote tumor angiogenesis by releasing VEGF, resulting in the creation of an immature and disorganized vascular network. The hypoxic microenvironment promoted by cancer cells favors the survival of more aggressive tumor cells, and gives rise to a challenging environment for immune cells to respond appropriately. As a result, VEGF has become a well-known target for anti-cancer drugs like bevacizumab. Bevacizumab Biosimilar is a mAb that exerts its effects by binding and inactivating serum VEGF. When bound to the mAb, VEGF is unable to interact with its cell surface receptors, and proangiogenic signalling is inhibited. This prevents formation of new blood vessels, decreases tumor vasculature, and reduces tumor blood supply. VEGF receptors are divided into three main categories: tyrosine kinase receptors (VEGFRs), neurocilia receptors (Neuropilins, NRPs), and Heparan sulfate proteoglycans (HSPGs). VEGF family protein members are selective in binding to VEGF receptors.

Figure2：Schematic structure of the VEGFRs.

VEGF Receptors (VEGFRs) are divided into VEGFR-1, VEGFR-2 and VEGFR-3. They act in the form of dimers. Vascular endothelial growth factor receptor 1 (VEGFR1) is also known as Fms-like tyrosine kinase 1 (FLT-1), Tyrosine-protein kinase receptor FLT, is a single-pass type I membrane protein and secreted protein that belongs to the protein kinase superfamily, the Tyr protein kinase family and the CSF-1/PDGF receptor subfamily. VEGFR1 is detected in normal lung, but also in the placenta, liver, order, heart and brain apkins and is specifically expressed in most of the vascular endothelial cells, and also in peripheral blood monocytes. VEGFR1, as a cell-surface receptor for VEGFA, VEGFB and PGF, plays an essential part in the development of embryonic vasculature, regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. VEGFR1 may play an important role as a negative regulator of embryonic angiogenesis by inhibiting the excessive proliferation of endothelial cells. VEGFR1 promotes endothelial cell proliferation, survival and angiogenesis in adulthood. VEGFR-2, the major signal transducer for angiogenesis, preferentially utilizes the PLCγ-PKC-MAPK pathway for signaling. The VEGF-VEGFR system is an important target for anti-angiogenic therapy in cancer and is also an attractive system for pro-angiogenic therapy in the treatment of neuronal degeneration and ischemic diseases.

NRPs (Neuropilins) are divided into NRP-1 and NRP-2. NRPs are single-shot transmembrane glycoproteins with 3 extracellular domains, domain B is the VEGF binding region, and domain A can promote the binding of domain B to VEGF. Domain C binds to VEGFR-2 to form heteropolymers. NRPs have no tyrosine kinase activity and mainly assist VEGF in binding to VEGFR-2. NRP-1 is mainly involved in the regulation of arterial endothelial function, while NRP-2 is mainly involved in the regulation of venous and lymphatic endothelial function.

 HSPGs (Heparan Sulfate Proteoglycans) consist of a core protein and one or more covalently linked heparin sulfate protein chains. Together with NRPs, it is considered to be a co-receptor of VEGF, which promotes more effective binding of VEGF to VEGFR2 and enhances the stability of receptor complexes.

The Mechanism of Action of Bevacizumab Biosimilar:

As a recombinant monoclonal antibody targeting VEGF, bevacizumab biosimilar can specifically bind to VEGF-A and block the combination of VEGF and VEGFR, thereby inhibiting angiogenesis and tumor growth, recurrence, and metastasis. That is to say, Bevacizumab can function as an angiogenesis inhibitor.

The VEGFR-1 (Flt-1) gene expresses 2 mRNAs: one is a long form of approximately 8 kb, and the other is a short form of 2.5 to 3.0 kb. The short mRNA is highly expressed in normal placenta, encoding a soluble form of Flt-1 known as sFlt-1. The sFlt-1 contains 6 Ig-like domains with a short, 31 amino acid–long tail derived from the 5′ region of intron 13 and exhibits a strong binding ability to VEGF-A, PlGF, and VEGF-B. Within the placenta, trophoblasts located between the fetal and maternal blood vessel systems preferentially express sFlt-1 (Fig. 3). Thus, an interesting possibility is that sFlt-1 functions as a biochemical barrier between fetal and maternal circulation in the placenta by suppressing excess angiogenesis and abnormal vascular permeability.

Figure3：The VEGF and VEGFR system.

Alpha Lifetech Inc. can provide research-grade Bevacizumab Biosimilar, which can be used for different applications: FC (Flow Cytometry), IP(Immunoprecipitation), ELISA(Enzyme-linked Immunosorbent Assay), Neut (Neutralization), FuncS (Functional Assay), IF (Immunofluorescence), ICC (Immunocytochemistry), etc.

Most biosimilars supplied by Alpha Lifetech Inc. have high purity, low endotoxin level and active data. Please don't hesitate to contact our customer representative to get a quote to accelerate your research.