The discovery of novel vascular endothelial growth factor receptor tyrosine kinases inhibitors: pharmacophore modeling, virtual screening and docking studies.

摘要: We have applied pharmacophore generation, database searching and docking methodologies to discover new structures for the design of vascular endothelial growth factor receptors, tyrosine kinase insert domain-containing receptor inhibitors. The chemical function based models were built inhibitors from a set 10 known using algorithm HipHop, which is implemented in CATALYST software. highest scoring HipHop model consists four features: one hydrophobic, hydrogen bond acceptor, donor ring aromatic function. Using CatShape within CATALYST, bound conformation 4-amino-furo [2, 3-d] pyrimidine binding was used generate shape query. A merged hypothesis query that an appropriate alignment then built. combined as search Maybridge other potential lead compounds. total 39 compounds retrieved hits. hits obtained docked into active site. One novel proposed on fit value, LigandFit scores, examination how hit retain key interactions be required binding. This compound inhibited stimulated phosphorylation human umbilical vein cells.