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In silico molecular docking, pharmacophore and 3D QSAR studies on Mer receptor tyrosine kinase inhibitors

KrishiKosh

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Title In silico molecular docking, pharmacophore and 3D QSAR studies on Mer receptor tyrosine kinase inhibitors
 
Creator Mishra, Adyasha
 
Contributor Pradhan, S K
 
Subject Receptor Tyrosine Kinases, pharmacophore, 3D-QSAR, HBA, HBD
 
Description Mer is a member of TAM (Tyro3, Axl, Mer) subfamily of Receptor Tyrosine Kinases, the
abnormal activation or overexpression of which has been implicated in survival signalling of
many human cancers. Inhibition of this Mer kinase may enhance the sensitivity of cancer cell
to cytotoxic agents and would potentially be a therapeutic strategy to target cancer cells. By
characterizing different lead inhibitors, the researchers had solved different crystal structures
of these Mer kinases with and without inhibitors, which is beneficial in the field of Structure
Based Drug Design of Mer kinase inhibitors. In silico molecular docking with three
dimensional pharmacophore and quantitative structure-activity relationship (3D-QSAR)
studies have been carried out using different sets of inhibitors of Mer kinase. The binding
pose of different inhibitors at active site amino acid residues of Mer RTK can be observed
from the docking studies. From the results of Rigid docking using Glide XP, top compounds
from each set were subjected to Induced fit docking, which show the compound 8 and 2 from
the first set and Compound 44 and 43 from the second set have good docking score, glide
energy and good interactions in comparison with other compounds as well as the co-crystal.
The pharmacophore and 3D QSAR studies have resulted in five point pharmacophore models
with one hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD), one hydrophobic
group(H) two aromatic rings(R) are used to derive a predictive atom-based 3D-QSAR model.
The best alignment was with Compound 20 and the good co-relation co-efficient and other
values with the training and test sets are R2=0.985, SD=0.160, F=423.1, Q2=0.634,
RMSE=0.632, Pearson-R=0.825. The results indicate that compound 20 is a good inhibitor
and further discovery of novel lead molecules for the inhibition of Mer RTK and can be done
from the proposed pharmacophore model.
 
Date 2017-01-04T14:15:01Z
2017-01-04T14:15:01Z
2015
 
Type Thesis
 
Identifier http://krishikosh.egranth.ac.in/handle/1/94458
 
Language en
 
Relation Th;4346
 
Format application/pdf