scholarly journals Discovery of novel picolinamide-based derivatives as novel VEGFR-2 kinase inhibitors: synthesis, in vitro biological evaluation and molecular docking

MedChemComm ◽  
2018 ◽  
Vol 9 (6) ◽  
pp. 1054-1058
Author(s):  
Wuji Sun ◽  
Shubiao Fang ◽  
Hong Yan
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Molecular Docking ◽  
Growth Factor ◽  
Cancer Therapy ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Biological Evaluation ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has emerged as an attractive target for cancer therapy.

scholarly journals Discovery of Small Molecules that Target Vascular Endothelial Growth Factor Receptor-2 Signalling Pathway Employing Molecular Modelling Studies

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 269 ◽  
Author(s):  
Shailima Rampogu ◽  
Ayoung Baek ◽  
Chanin Park ◽  
Shraddha Parate ◽  
Saravanan Parameswaran ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Molecular Docking ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Pharmacophore Model ◽  
Docking Studies ◽  
Vascular Endothelial ◽  
Molecular Docking Studies ◽  
Angiogenic Inhibitors ◽  
Endothelial Growth Factor

Angiogenesis is defined as the formation of new blood vessels and is a key phenomenon manifested in a host of cancers during which tyrosine kinases play a crucial role. Vascular endothelial growth factor receptor-2 (VEGFR-2) is pivotal in cancer angiogenesis, which warrants the urgency of discovering new anti-angiogenic inhibitors that target the signalling pathways. To obtain this objective, a structure-based pharmacophore model was built from the drug target VEGFR-2 (PDB code: 4AG8), complexed with axitinib and was subsequently validated and employed as a 3D query to retrieve the candidate compounds with the key inhibitory features. The model was escalated to molecular docking studies resulting in seven candidate compounds. The molecular docking studies revealed that the seven compounds displayed a higher dock score than the reference-cocrystallised compound. The GROningen MAchine for Chemical Simulations (GROMACS) package guided molecular dynamics (MD) results determined their binding mode and affirmed stable root mean square deviation. Furthermore, these compounds have preserved their key interactions with the residues Glu885, Glu917, Cys919 and Asp1046. The obtained findings deem that the seven compounds could act as novel anti-angiogenic inhibitors and may further assist as the prototype in designing and developing new inhibitors.

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