title: Combination of pharmacophore hypothesis, genetic function approximation model, and molecular docking to identify novel inhibitors of S6K1.
abstract: S6K1 has emerged as a potential target for the treatment for obesity, type II diabetes and cancer diseases. Discovery of S6K1 inhibitors has thus attracted much attention in recent years. In this investigation, a hybrid virtual screening method that involves pharmacophore hypothesis, genetic function approximation (GFA) model, and molecular docking technology has been used to discover S6K1 inhibitors especially with novel scaffolds. The common feature pharmacophore hypothesis and GFA regression model of S6K1 inhibitors were first developed and applied in a virtual screen of the Specs database for retrieving S6K1 inhibitors. Then, the molecular docking method was carried out to re-filter these screened compounds. Finally, 60 compounds with promising S6K1 inhibitory activity were carefully selected and have been handed over to the other group to complete the follow-up compound synthesis (or purchase) and activity test.
authors: College of Life Science, Northwest Normal University, Lanzhou , 730070, Gansu, People's Republic of China, zhanghui123gansu@163.com.
authors: Hui
authors: H
authors: Zhang
authors: Ming-Li
authors: ML
authors: Xiang
authors: Jun-Yu
authors: JY
authors: Liang
authors: Tao
authors: T
authors: Zeng
authors: Xiao-Nuo
authors: XN
authors: Zhang
authors: Ji
authors: J
authors: Zhang
authors: Sheng-Yong
authors: SY
authors: Yang
mesh_terms: D016208:Databases, Factual; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
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