INSILICO ANALYSIS OF DIETARY AGENTS AS ANTICANCER INHIBITORS OF INSULIN LIKE GROWTH FACTOR 1 RECEPTOR (IGF1R)
Keywords:
IGF-1R Inhibitors, Dietary agents, Insilico modeling, Binding affinities, Molecular DockingAbstract
Objective: Insulin-like growth factor 1 receptor (IGF-1R) is over-expressed in a number of cancer cell lines and has been implicated to play a role in oncogenesis and suppression of apoptosis. Thus, the inhibition of IGF-1R activity leads to tumor regression and renders IGF-1R a plausible target for the development of anti-cancer drugs. Dietary agents are known to interfere with IGF signaling and offer a foundation for developing nontoxic agents that override any toxicity associated with synthetic IGF inhibitors. This study is designed to obtain structural motifs and active residues that preferentially interact with IGF1Rand to identify the phytochemicals from different plants and act as potential anticancer drug leads
Methods: Thus, six dietary agents known to interfere directly with circulating levels of IGF1R were undertaken for docking studies. A molecular docking simulation model of IGF1R with its bound ligand was established and validated to be used as a reference model for the study.
Results: The active site residuesGLU1080, MET 1082, GLU1081, GLU1027, GLU1145 and ARG1003 were found to play a significant role in binding mechanism. The ADME properties and drug likeliness of the ligands were rigorously analyzed under four criteria of known successful drug activity in the areas of GPCR ligand activity, ion channel modulation, kinase inhibition activity, nuclear receptor ligand activity and enzyme inhibition. The dietary agents Apigenin and Luteolin demonstrated reliable interaction with IGF1R (-5.78Kcal/mol and-5.70 Kcal/mol respectively)and displayed good pharmacokinetics properties.
Conclusion: It is concluded that the explored dietary agents offer profound promise to be used natural inhibitors of IGF1R and thus may be useful for the preparation of different combinations and formulations for the management of tumors.
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References
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