Structure-based optimization of tyrosine kinase inhibitors: a molecular docking study

AbstractThe most common pharmacologic approaches to inhibiting EGFR have been to develop small-molecule inhibitors which exert their effects at the intracellular portion of the receptor to prevent tyrosine kinase phosphorylation and subsequent activation of signal transduction pathways. A non-covalent molecular docking study was carried-out between 119 NCI anticancer compounds with receptor tyrosine kinase domain from epidermal growth factor receptor (PDB ID: 1M14), out of which 11 compounds had binding energy calculated with monte Carlo algorithm in ICM-pro Molsoft< − 25.25 kcal/mol. was found to have highest binding affinity with a reported value of − 32.832 kcal/mol, while Asaley had the overall least value (− 1.977 kcal/mol). The binding energy of all the compounds were found to be greatly influenced by the number and type of hydrogen bond i nteraction present between the ligands and the receptor except in few instances involving 5-flourouracil and mitomycin. A detailed description of the interactions of EGFR inhibitors developed can assist in the design of a more potent, more specific cytostatic drugs that can arrest tumor growth and c ause tumor regression.

Source: Network Modeling Analysis in Health Informatics and Bioinformatics - May 16, 2018 Category: Bioinformatics Source Type: research