Vascular Endothelial Growth Factor Receptor Kinase 2 (VGFR-2) Focused Library

The formation of new blood vessels from the existing vascular system is called angiogenesis. It is a fundamental physiological process for the cell growth, tissue repair, wound healing and reproductive system of females. The process of angiogenesis regulation is closely associated with diseases such as rheumatoid arthritis, diabetes mellitus, atherosclerosis and cancer. Tumor growth and metastasis are directly dependent on the process of tumor angiogenesis. The VEGF family and their corresponding receptor tyrosine kinases such as VEGFR-1, VEGFR-2 and VEGFR-3 play an essential and integral role in regulating several aspects of the angiogenic and lymphangiogenic processes as well as in inducing vascular permeability and inflammation. Expression of VEGFs by tumor cells is a significant mark of many human and rodent tumors in vivo, and is associated with tumor growth rate, microvessel density/proliferation in a variety of malignancies. Diverse VEGFR inhibitors such as soluble receptors, anti-VEGF and anti-VEGFR-2 antibodies, and VEGF transcriptional inhibitors can disrupt the VEGF/VEGFR signaling cascade, and many anti-VEGFR-2 antibodies are currently in clinical development.

BOC Sciences can develop a reliable VGFR-2 focused library to produce potential VEGFR-2 type II inhibitors.

Figure 1. The signaling pathways of VEGFs/VEGFRs and their biological functions. (Ming, H.; et al. 2019)

Library Design

Compared to type I kinase inhibitors, type II kinase inhibitors are able to improve kinase selectivity and reduce the rates. Therefore, BOC Sciences is focused on creating a VGFR-2 focused library for the identification of type II VEGFR kinase inhibitors that enable to bind to kinase in DFG-out conformation of the activation loop.

1. Firstly, we have created a protein docking model of the protein based on the crystal structure documented in the PDB entry, and the key amino acid that are responsible for hydrogen bond of the ligand is set to Cys919 from the hinge region, and also conserved Glu885 and Asp1046. Two hydrophobic regions of the VEGFR-2 binding site are identified and included in the docking constraint:
2. Then, we set up a series of docking programs to perform molecular docking and subsequent analysis of the docking results
3. BOC Sciences also supports GROMACS software to conduct molecular dynamics (MD) simulations and preparation of protein structures, in which ligand molecules are processed
4. Only compounds meeting Lipinski and Veber rules are able to be selected for docking screening

Figure 2. The function roles of VEGF-C/VEGFR3 signaling in tumor progression. (Ming, H.; et al. 2019)

Vascular Endothelial Growth Factor Receptor Kinase 2 (VGFR-2) Focused Library Characteristics

• Favorable physicochemical parameters and solubility requirements
• No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
• Bioactivity and safety confirmed by preclinical studies and clinical trials
• Structural diversity, medicinal activity, and cellular penetration
• Structural document, IC₅₀, and other chemical and biological data are provided
• All compounds are continually updated
• Compound cherry-picking service is provided

What We Deliver

• Delivered within 2 weeks in any customer-preferred format
• Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
• All compounds have a minimum purity of 90% assessed by ¹H NMR and HPLC
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Vascular Endothelial Growth Factor Receptor Kinase 2 (VGFR-2) Focused Library design at competitive prices for global customers. Personalized and customized services of Vascular Endothelial Growth Factor Receptor Kinase 2 (VGFR-2) Focused Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!