Table 1.
Recent examples of fragment-based screening.
| Reference | Article title | Target protein | Primary/secondary FBDD screening method | Binding/activity assay |
|---|---|---|---|---|
| [54,55] | Application of Fragment Screening by X-ray Crystallography to the Discovery of Aminopyridines as Inhibitors of -Secretase | β-Secretase | X-ray crystallography | Fluorescence-based activity assay |
| [56] | Missing fragments: detecting cooperative binding in fragment-based drug design | hPNMT | X-ray crystallography | ITC/Molecular dynamics free energy calculation |
| [57] | Fragment-based screening for inhibitors of PDE4A using enthalpy arrays and X-ray crystallography | Phosphodiesterase 4A | High-throughput calorimetry/X-ray crystallography | High-throughput calorimetry |
| [58,59] | Fragment-Based Drug Discovery Applied to Hsp90. Discovery of Two Lead Series with High Ligand Efficiency | Hsp90 | NMR/X-ray crystallography | ITC/Bioassay |
| [60] | Fragment-Based Discovery of Bromodomain Inhibitors Part 1: Inhibitor binding modes and implications for lead discovery | Bromodomain | Fluorescence anisotropy assay/X-ray crystallography | Fluorescence anisotropy assay |
| [61] | Fragment-Based Discovery of Bromodomain Inhibitors Part 2: Optimization of Phenylisoxazole Sulfonamide | Bromodomain/AcK pocket | Fluorescence anisotropy assay/Modelling X-ray crystallography | SPR/Thermal shift assay |
| [62] | Structure-based design of potent and ligand-efficient inhibitors of CTX-M class A β-lactamase | β-lactamase CTX-M | Docking/X-ray crystallography | UV-absorbance based bioassays/Antibacterial activity |
| [63] | Discovery of 1,2,4-triaine derivatives as adenosine A2A antagonists using structure based drug design | Adenosine A2 receptor | Docking/X-ray crystallography | SPR |
| [64] | Discovery and Optimization of New Benzimidazole- and Benzoxazole-Pyrimidone Selective PI3Kβ Inhibitors for the Treatment of Phosphatase and TENsin homologue (PTEN)-Deficient Cancers | PI3K | In vitro enzyme assay/Cell based assay X-ray crystallography | In vitro enzyme assay/Cell-based assay |
| [65] | Synthesis, Structure–Activity Relationship Studies, and X-ray Crystallographic Analysis of Arylsulfonamides as Potent Carbonic Anhydrase Inhibitor | Carbonic anhydrases | Docking/X-ray crystallography | Stopped-flow kinetic assay |
| [66] | Implications of Promiscuous Pim-1 Kinase Fragment Inhibitor Hydrophobic Interactions for Fragment-Based Drug Design | Pim-1 Kinase | Docking/X-ray crystallography | Mobility shift assay |