A dataset containing the experimental values of the equilibrium binding constants of clinical drugs, and some other organic ligands with human and mammalian (predominantly bovine) serum albumins, is assembled. The affinity of drugs to albumin governs their pharmacokinetic properties, related to permeability through physiological barriers and distribution within the organism. The dataset contains 1755 records gathered from 346 original literature sources describing the albumin affinity of 324 different substances. The data were extracted from both articles and existing protein-binding databases applied strict data selection rules in order to exclude the values influenced by the third-party compounds. The dataset provides the details on the experimental conditions of the measurements, such as temperature; protein and ligand concentrations; buffer pH, composition and concentration; and the method and model used for the binding constant calculations. Analysis of the data reveals discrepancies between the values from different studies, as well as the significant influence of the measurement method. Averaging the values from multiple independent measurements from the dataset may help to determine the reliable values of the binding constants. The dataset can be used as the reference dataset for the development of predictive models to calculate binding constants, and as the choice for the experimental setup in the future albumin-binding studies.

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Experimental data on the affinity of various substances to albumin are essential for the development of empirical models to predict plasma binding of drug candidates. Binding of 24 substituted benzoic acid anions to bovine serum albumin was studied using spectrofluorimetric titration. The equilibrium constants of binding at 298 K were determined according to 1:1 complex formation model. The relationships between the ligand structure and albumin affinity are analyzed. The binding constant values for m- and p-monosubstituted acids show a good correlation with the Hammett constants of substituents. Two- and three-parameter quantitative structure–activity relationship (QSAR) models with theoretical molecular descriptors are able to satisfactorily describe the obtained values for the whole set of acids. It is shown that the electron-density distribution in the aromatic ring exerts crucial influence on the albumin affinity.

The ability to detect and monitor amyloid deposition in the brain using non-invasive imaging techniques provides valuable insights into the early diagnosis and progression of Alzheimer’s disease and helps to evaluate the efficacy of potential treatments. Magnetic resonance imaging (MRI) is a widely available technique offering high-spatial-resolution imaging. It can be used to visualize amyloid deposits with the help of amyloid-binding diagnostic agents injected into the body. In recent years, a number of amyloid-targeted MRI probes have been developed, but none of them has entered clinical practice. We review the advances in the field and deduce the requirements for the molecular structure and properties of a diagnostic probe candidate. These requirements make up the base for the rational design of MRI-active small molecules targeting amyloid deposits. Particular attention is paid to the novel cryo-EM structures of the fibril aggregates and their complexes, with known binders offering the possibility to use computational structure-based design methods. With continued research and development, MRI probes may revolutionize the diagnosis and treatment of neurodegenerative diseases, ultimately improving the lives of millions of people worldwide.

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