Structure-Based Virtual Screening for the Identification of High Affinity Compounds as Potent VEGFR2 Inhibitors for the Treatment of Renal Cell Carcinoma

Title:Structure-Based Virtual Screening for the Identification of High Affinity Compounds as Potent VEGFR2 Inhibitors for the Treatment of Renal Cell Carcinoma

Volume: 18 Issue: 25

Author(s): Khushboo Sharma, Khushboo Patidar, Meer Asif Ali, Pravin Patil, Himshikha Goud, Tajamul Hussain, Anuraj Nayarisseri*Sanjeev Kumar Singh*

Affiliation:

• In silico Research Laboratory, Eminent Biosciences, Vijayanagar, Indore – 452010, Madhya Pradesh,India

• Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi-630 003, Tamil Nadu,India

Keywords: VEGFR2, Renal cell carcinoma, Virtual screening, Drug designing, Molecular docking, Cancer.

Abstract: Introduction: Renal Cell Carcinoma is a common type of renal cancer-causing deaths worldwide which is characterized by sustained angiogenesis. VEGF and its receptors play a major role in physiologic and pathologic angiogenesis, which is marked in tumour progression and metastasis development. Induction of VEGF genes occur due to hypoxic condition induced by tumour growth after a critical size in cancerous cell. Signal transduction networks originated by VEGFA/VEGFR2, (a notable ligand-receptor complex in the VEGF system) leads to major angiogenesis events ranging from endothelial cell proliferation, to new vessel formation, Furthermore, differential expression of VEGF-VEGFR mRNA also found in different types of RCC.

Aim: The aim of present study is to inhibit the VEGFR2 protein by the action of certain inhibitors and then to search an efficient inhibitor.

Materials and Methods: A total of 23 potential inhibitors were searched and used to target the protein using the concept of molecular docking. Among 23 inhibitors, CHEMBL346631 shows best affinity with the target protein and was used for high throughput virtual screening to find similar compounds. The compound obtained from virtual screeningSCHEMBL469307, shows much more better affinity with VEGFR2 than CHEMBL346631.

Conclusion: Relative study for both the compounds showed a minor difference in relevant properties. The compound SCHEMBL469307 have a high potential to inhibit the VGFR2 protein and can be backed for future studies in Renal Cell Carcinoma.

Cite this article as:

Sharma Khushboo, Patidar Khushboo, Ali Asif Meer , Patil Pravin , Goud Himshikha , Hussain Tajamul , Nayarisseri Anuraj *, Singh Kumar Sanjeev *, Structure-Based Virtual Screening for the Identification of High Affinity Compounds as Potent VEGFR2 Inhibitors for the Treatment of Renal Cell Carcinoma, Current Topics in Medicinal Chemistry 2018; 18 (25) . https://dx.doi.org/10.2174/1568026619666181130142237