title: Evolutions in fragment-based drug design: the deconstruction-reconstruction approach.
abstract: Recent advances in the understanding of molecular recognition and protein-ligand interactions have facilitated rapid development of potent and selective ligands for therapeutically relevant targets. Over the past two decades, a variety of useful approaches and emerging techniques have been developed to promote the identification and optimization of leads that have high potential for generating new therapeutic agents. Intriguingly, the innovation of a fragment-based drug design (FBDD) approach has enabled rapid and efficient progress in drug discovery. In this critical review, we focus on the construction of fragment libraries and the advantages and disadvantages of various fragment-based screening (FBS) for constructing such libraries. We also highlight the deconstruction-reconstruction strategy by utilizing privileged fragments of reported ligands.
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, PR China; Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Haijun
authors.initials: H
authors.lastname: Chen
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, PR China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, PR China.
authors.forename: Ailan
authors.initials: A
authors.lastname: Wang
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, PR China.
authors.forename: Yunquan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: jizhou@utmb.edu.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
mesh_terms: D015195:Drug Design; D005941:Glucokinase / Q000378:metabolism; D008024:Ligands; D050479:Neurotransmitter Transport Proteins / Q000037:antagonists & inhibitors; D018091:Receptors, AMPA / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D054852:Small Molecule Libraries; D000097605:Sigma-1 Receptor
chemical_list: D005941:Glucokinase; D008024:Ligands; D050479:Neurotransmitter Transport Proteins; D018091:Receptors, AMPA; D017480:Receptors, sigma; D050796:STAT3 Transcription Factor; D054852:Small Molecule Libraries; D000097605:Sigma-1 Receptor