title: Pharmacophore modelling, molecular docking and virtual screening for EGFR (HER 1) tyrosine kinase inhibitors.
abstract: A pharmacophore model has been developed using diverse classes of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors useful in the treatment of human tumours. Among the top 10 generated hypotheses, the second hypothesis, with one hydrogen bond acceptor, one ring aromatic and three hydrophobic features, was found to be the best on the basis of Cat Scramble validation as well as test set prediction (r(training) = 0.89, r(test) = 0.82). The model also maps well to the external test set molecules as well as clinically active molecules and corroborates the docking studies. Finally, 10 hits were identified as potential leads after virtual screening of ZINC database for EGFR TK inhibition. The study may facilitate the designing and discovery of novel EGFR TK inhibitors.
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Gupta
authors.forename: S S
authors.initials: SS
authors.lastname: Bhunia
authors.forename: V M
authors.initials: VM
authors.lastname: Balaramnavar
authors.forename: A K
authors.initials: AK
authors.lastname: Saxena
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases