title: Novel EGFR (T790M)-cMET dual inhibitors: putative therapeutic agents for non-small-cell lung cancer.
abstract: Different resistance mechanisms, especially, T790M secondary acquired point mutation and in some cases amplification of cMET, have been a major setback for the lung cancer therapies.
  
  
  
  The current in silico study explored the small molecules which can act as putative EGFR (T790M)-cMET dual inhibitors. Databases were first filtered and subsequently cross filtered, initially by thoroughly validated pharmacophore models for both targets. As per score and interactions obtained in docking, the molecules were subjected to molecular dynamics simulations, to study the stability and binding orientations of their complexes with target proteins.
  
  
  
  Molecular dynamics simulations predicted three hits to possess good binding affinities and stability for EGFR (T790M) and cMET, which can be claimed to be potential dual inhibitors.
authors.affiliation: Molecular Modelling Lab (MML), Department of Pharmaceutical Sciences and Drug research, Punjabi University, Patiala, Punjab 147002, India.
authors.forename: Pankaj Kumar
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Molecular Modelling Lab (MML), Department of Pharmaceutical Sciences and Drug research, Punjabi University, Patiala, Punjab 147002, India.
authors.forename: Om
authors.initials: O
authors.lastname: Silakari
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; C512478:EGFR protein, human; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met
keywords: EGFR (T790M); cMET; lung cancer; molecular dynamics; pharmacophore