Titel
Investigating experimental vs. Predicted pKa values for PET radiotracer
Autor*in
Sarah Luise Stellnberger
Verena Schwingenschlögl-Maisetschläger
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Abstract
The prediction of central nervous system (CNS) active pharmaceuticals and radiopharmaceuticals has experienced a boost by the introduction of computational approaches, like blood–brain barrier (BBB) score or CNS multiparameter optimization values. These rely heavily on calculated pKa values and other physicochemical parameters. Despite the inclusion of various physicochemical parameters in online data banks, pKa values are often missing and published experimental pKa values are limited especially for radiopharmaceuticals. This comparative study investigated the discrepancies between predicted and experimental pKa values and their impact on CNS activity prediction scores. The pKa values of 46 substances, including therapeutic drugs and PET imaging radiopharmaceuticals, were measured by means of potentiometry and spectrophotometry. Experimentally obtained pKa values were compared with in silico predictions (Chemicalize/Marvin). The results demonstrate a considerable discrepancy between experimental and in silico values, with linear regression analysis showing intermediate correlation (R2(Marvin) = 0.88, R2(Chemicalize) = 0.82). This indicates that if one requires an accurate pKa value, it is essential to experimentally assess it. This underscores the importance of experimentally determining pKa values for accurate drug design and optimization. The study’s data provide a valuable library of reliable experimental pKa values for therapeutic drugs and radiopharmaceuticals, aiding researchers in the field.
Stichwort
Ionization constantCentral nervous systemRadiotracer
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
phaidra.univie.ac.at/o:2114292
Erschienen in
Titel
European Journal of Pharmaceutics and Biopharmaceutics
Band
203
ISSN
0939-6411
Erscheinungsdatum
2024
Publication
Elsevier BV
Erscheinungsdatum
2024
Zugänglichkeit
Rechte
Rechteangabe
© 2024 The Author(s)
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