Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Chemistry, Medicinal, Pharmacology & Pharmacy, Computer-aided drug design, Ligand-based drug design, Structure-based drug design, positron emission tomography (PET), single photon emission tomography (SPECT), Absorption-distribution-metabolism-excretion toxicity (ADMET), PROTEIN-LIGAND DOCKING, SMALL-ANIMAL-MODELS, MOLECULAR-DOCKING, DRUG DESIGN, CRYSTAL-STRUCTURE, MEMBRANE ANTIGEN, PREDICTION, PET, DISCOVERY, TOOLS, Absorption-distribution-metabolism-excretiontoxicity (ADMET), Computer-Aided Design, Drug Design, Molecular Docking Simulation, Molecular Probes, Peptides, Radiopharmaceuticals, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3214 Pharmacology and pharmaceutical sciences, 3404 Medicinal and biomolecular chemistry

Abstract:

This review describes the usefulness of in silico design approaches in the design of new radiopharmaceuticals, especially peptide-based radiotracers (including peptidomimetics). Although not part of the standard arsenal utilized during radiopharmaceutical design, the use of in silico strategies is steadily increasing in the field of radiochemistry as it contributes to a more rational and scientific approach. The development of new peptide-based radiopharmaceuticals as well as a short introduction to suitable computational approaches are provided in this review. The first section comprises a concise overview of the three most useful computeraided drug design strategies used, namely i) a Ligand-based Approach (LBDD) using pharmacophore modelling, ii) a Structure-based Design Approach (SBDD) using molecular docking strategies and iii) Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) predictions. The second section summarizes the challenges connected to these computer-aided techniques and discusses successful applications of in silico radiopharmaceutical design in peptide-based radiopharmaceutical development, thereby improving the clinical procedure in Nuclear Medicine. Finally, the advances and future potential of in silico modelling as a design strategy is highlighted.