Structure-Based Virtual Screening, Molecular Docking, and Molecular Dynamics Simulation of VEGF inhibitors for the clinical treatment of Ovarian Cancer

Abstract

Vascular Endothelial Growth Factor (VEGF) and its receptor play an important role both in physiologic and pathologic angiogenesis, which is identi ed in ovarian cancer progression and metastasis development. The aim of the present investigation is to identify a potential Vascular Endothelial Growth Factor inhibitor which is playing a crucial role in stimulating the immunosuppressive microenvironment in tumour cells of the ovary and to examine for an effectiveness of identi ed inhibitor for the treatment of ovarian cancer using various in-silico approaches. 12 established VEGF inhibitors were collected from various literature. The compound AEE788 displays the great a nity towards the target protein as a result of docking study. AEE788 was further used for structure-based virtual screening in order to obtain a more structurally similar compound with high a nity. Among the 80 Virtual screened compounds, CID 88265020, explicates much better a nity than established compound AEE788. Based on Molecular Dynamics Simulation, pharmacophore and comparative toxicity analysis of both the best-established compound and the best virtual screened compound displayed a trivial variation in associated properties. The virtual screened compound CID 88265020 have a high a nity with the lowest re-rank score, and holds a huge potential to inhibit the VGFR and can be implemented for prospective future investigations in Ovarian Cancer.

SPOCK2 Promotes the Malignant Behavior of Ovarian Cancer via Regulation of the Wnt/β-Catenin Signaling Pathway

“…Targeted therapy causes specific death of cancer cells by binding targeted drugs to specific cancer sites without affecting surrounding normal tissue cells [18]. Currently, targeted therapeutic agents that have been used in ovarian cancer include olaparib and niraparib, VEGF inhibitors, and the antiangiogenesis inhibitor bevacizumab, but the above-targeted agents are less used in clinical practice because of their narrow indications, high prices, and certain adverse effects [19][20][21]. Exploring the molecular mechanisms associated with ovarian cancer progression is the basis for developing novel diagnostic and therapeutic approaches for ovarian cancer.…”

In vitro and in silico Investigations on the Anti-cancer Efficacy of Eupatorin, a Polymethoxy Flavone against Ovarian Cancer PA-1 Cell Line

“…21,29 Vascular Endothelial Growth Factor (VEGF) and its receptor are interesting targets for the development of anticancer drugs because they are crucial in both pathologic and physiological angiogenesis. 30 Therefore, the VEGF-A/VEGFR complex was chosen as the target to study Eupatorin's binding. To ascertain the precise posture and position of Eupatorin binding as well as the interactions relevant to the binding occurrence, docking experiments were conducted by considering the ligand and the binding site residues as flexible.…”

Identification of promising nutraceuticals against filarial immune-modulatory proteins: insights from in silico and ex vivo studies

“…25,26 Further, absorption, distribution, metabolism, excretion, and toxicity (ADMET) were analyzed using admetSAR. 27,28 Also, the canonical SMILES of ligands were taken from the PubChem database and copied into the admetSAR server.…”