title: Identification of triazolo[4,5-b]pyrazine derivatives as hepatocyte growth factor receptor inhibitors through structure-activity relationships and molecular docking simulations.
abstract: c-MET is a receptor tyrosine kinase and potential oncological target for cancer therapy. The activities of 1,2,3-triazolo[4,5-b]pyrazine series of c-MET inhibitors were analyzed according to the three-dimensional quantitative structure-activity relationship and molecular docking methods. The results indicated that the hydrophobic and electrostatic fields play key roles in activity and QSAR model was reliable enough for activity prediction. Moreover, the docking results do validate the predicted 3D-QSAR scores, vital residues Asp1222, Asp1231, Met1160, Tyr1259 and Tyr1230 found in binding site. Four new c-MET inhibitor analogs designed in this Letter which are being currently synthesized by our laboratories.
authors: School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, PR China.
authors: Minghui
authors: M
authors: Dong
authors: School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, PR China. Electronic address: clab@sit.edu.cn.
authors: Yujie
authors: Y
authors: Ren
authors: School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, PR China.
authors: Xiaodong
authors: X
authors: Gao
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011719:Pyrazines; D014230:Triazoles; C000607755:triazolo(4,5-b)pyrazine; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: 3D-QSAR; Analogs design; Cancer therapy; Molecular docking; c-MET