Identification of Potent VEGF Inhibitors for the Clinical Treatment of Glioblastoma, A Virtual Screening Approach.
Mohini YadavRavina KhandelwalUrvy MudgalSivaraj SrinithaNatasha KhandekarAnuraj NayarisseriSugunakar VureeSanjeev Kumar SinghPublished in: Asian Pacific journal of cancer prevention : APJCP (2019)
Vascular endothelial growth factor (VEGF) expression could be found in all glioblastomas. VEGF takes part in
numerous changes including the endothelial cell proliferation, the vasculature of solid tumor: its survival invasion,
and migration, chemotaxis of bone marrow-derived progenitor cells, vasodilation and vascular permeability. VEGF
inhibition can be a smart therapeutic strategy because it is extremely specific and less toxic than cytotoxic therapy. To
establish better inhibition of VEGF than the current inhibitors, present study approach is by molecular docking, virtual
screening to illustrate the inhibitor with superior affinity against VEGF to have a cautious pharma profile. To retrieve
the best established and high-affinity high affinity molecule, Molegro Virtual Docker software was executed. The
high-affinity scoring compounds were subjected to further similarity search to retrieve the drugs with similar properties
from pubchem database. The completion of virtual screening reveals that PubChem compound SCHEMBL1250485
(PubChem CID: 66965667) has the highest affinity. The study of the drug-likeness was verified using OSIRIS Property
Explorer software which supported the virtual screened result. Further ADMET study and drug comparative study
strongly prove the superiority of the new established inhibitor with lesser rerank score and toxicity. Overall, the new
inhibitor has higher potential to stop the expression of VEGF in glioblastoma and positively can be further analysed
through In vitro studies.
Keyphrases
- vascular endothelial growth factor
- endothelial cells
- molecular docking
- cell proliferation
- poor prognosis
- emergency department
- oxidative stress
- long non coding rna
- mesenchymal stem cells
- bone marrow
- signaling pathway
- adverse drug
- binding protein
- smoking cessation
- capillary electrophoresis
- chemotherapy induced
- free survival
- replacement therapy
- case control