MOLECULAR DOCKING AND IN-SILICO ADME STUDIES OF NOVEL DERIVATIVE OF ERLOTINIB IN GLIOMAAbstract
Glioblastoma (GBM), with restricted therapy alternatives, is a catastrophic primary brain tumor. The receptor of the epidermal growth factor receptor (EGFR) in glioblastomas is recurrently enhanced, over articulated, or mutated, but up to 20 percent of GBM patients find it to be responded to kinase inhibition of EGFR. Several inhibitors of EGFR tyrosine kinase (TKI) failed clinically, due in part to acquired resistance. To automatically examine this type of resistance, we used molecular docking and swissADME approach to elucidate its putative inhibitor. We have attempted to determine a drug candidate in the current research based on the discovery of structural drugs. Docking simulation was conducted on mutated EFGR to determine the best drug candidate from Erlotinib, a renowned anti-cancer agent, derivatives. A total of 200 structures were selected for the 2D crystal structure of erlotinib based on molecular fingerprinting. Top 10 best-docked proteins were analyzed using UCSF Chimera and discovered the complicated atomic-scale properties between ligand and the target protein. SCHEMBL13087058 ligand selected based on hydrogen bonding with methionine and swissADME screening shown the drug likeliness of the molecule with Molecular docking results showed binding energy -14.29 kcal/mol. Further wet lab study requires to study the actual binding as compulsory mode provided. To discover new inhibitors of EGFR with higher potency and specificity, additional information is needed for future design molecules.
D. Tripathi and S. Imran *
Department of Biotechnology, Faculty of Engineering and Technology, Manav Rachna International Institute of Research and Studies, Faridabad, Haryana, India.
07 February 2020
15 March 2020
17 March 2020
01 May 2020