title: Pharmacophore modeling and virtual screening to identify potential RET kinase inhibitors.
abstract: Chemical features based 3D pharmacophore model for REarranged during Transfection (RET) tyrosine kinase were developed by using a training set of 26 structurally diverse known RET inhibitors. The best pharmacophore hypothesis, which identified inhibitors with an associated correlation coefficient of 0.90 between their experimental and estimated anti-RET values, contained one hydrogen-bond acceptor, one hydrogen-bond donor, one hydrophobic, and one ring aromatic features. The model was further validated by a testing set, Fischer's randomization test, and goodness of hit (GH) test. We applied this pharmacophore model to screen NCI database for potential RET inhibitors. The hits were docked to RET with GOLD and CDOCKER after filtering by Lipinski's rules. Ultimately, 24 molecules were selected as potential RET inhibitors for further investigation.
authors: Department of Computer Science, National Tsing Hua University, Hsinchu, Taiwan.
authors: Kuei-Chung
authors: KC
authors: Shih
authors: Chung-Wai
authors: CW
authors: Shiau
authors: Ting-Shou
authors: TS
authors: Chen
authors: Ching-Huai
authors: CH
authors: Ko
authors: Chih-Lung
authors: CL
authors: Lin
authors: Chun-Yuan
authors: CY
authors: Lin
authors: Chrong-Shiong
authors: CS
authors: Hwang
authors: Chuan-Yi
authors: CY
authors: Tang
authors: Wan-Ru
authors: WR
authors: Chen
authors: Jui-Wen
authors: JW
authors: Huang
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D051096:Proto-Oncogene Proteins c-ret