title: Data quality in drug discovery: the role of analytical performance in ligand binding assays.
abstract: Despite its importance and all the considerable efforts made, the progress in drug discovery is limited. One main reason for this is the partly questionable data quality. Models relating biological activity and structures and in silico predictions rely on precisely and accurately measured binding data. However, these data vary so strongly, such that only variations by orders of magnitude are considered as unreliable. This can certainly be improved considering the high analytical performance in pharmaceutical quality control. Thus the principles, properties and performances of biochemical and cell-based assays are revisited and evaluated. In the part of biochemical assays immunoassays, fluorescence assays, surface plasmon resonance, isothermal calorimetry, nuclear magnetic resonance and affinity capillary electrophoresis are discussed in details, in addition radiation-based ligand binding assays, mass spectrometry, atomic force microscopy and microscale thermophoresis are briefly evaluated. In addition, general sources of error, such as solvent, dilution, sample pretreatment and the quality of reagents and reference materials are discussed. Biochemical assays can be optimized to provide good accuracy and precision (e.g. percental relative standard deviation <10 %). Cell-based assays are often considered superior related to the biological significance, however, typically they cannot still be considered as really quantitative, in particular when results are compared over longer periods of time or between laboratories. A very careful choice of assays is therefore recommended. Strategies to further optimize assays are outlined, considering the evaluation and the decrease of the relevant error sources. Analytical performance and data quality are still advancing and will further advance the progress in drug development.
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, 38106, Brunswick, Germany. h.waetzig@tu-bs.de.
authors.forename: Hermann
authors.initials: H
authors.lastname: Wätzig
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, 38106, Brunswick, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Oltmann-Norden
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, 38106, Brunswick, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Steinicke
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, 38106, Brunswick, Germany.
authors.forename: Hassan A
authors.initials: HA
authors.lastname: Alhazmi
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, 38106, Brunswick, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Nachbar
authors.affiliation: Chemistry Department, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia.|Chemistry Department, Faculty of Science, Assiut University, Assiut, 71516, Egypt.
authors.forename: Deia Abd
authors.initials: DA
authors.lastname: El-Hady
authors.affiliation: Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, 80203, Saudi Arabia.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Albishri
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, 38106, Brunswick, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Baumann
authors.affiliation: Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Exner
authors.affiliation: Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Böckler
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, 38106, Brunswick, Germany.
authors.forename: Sami
authors.initials: S
authors.lastname: El Deeb
mesh_terms: D001681:Biological Assay / Q000592:standards*; D002151:Calorimetry / Q000592:standards; D000068598:Data Accuracy; D016208:Databases, Factual; D055808:Drug Discovery; D019075:Electrophoresis, Capillary / Q000592:standards; D005453:Fluorescence; D007118:Immunoassay / Q000592:standards; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D004364:Pharmaceutical Preparations / Q000378:metabolism; D012680:Sensitivity and Specificity; D020349:Surface Plasmon Resonance / Q000592:standards
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations
keywords: Biochemical assays; Cell-based assays; Databases; Drug discovery; Ligand binding assay; Precision