Radiolabeled HOCPCA as a highly useful tool in drug discovery and pharmacology

0541447 - ÚOCHB 2022 RIV GB eng J - Článek v odborném periodiku
Griem-Krey, N. - Frolund, B. - Marek, Aleš - Wellendorph, P.
Radiolabeled HOCPCA as a highly useful tool in drug discovery and pharmacology.
Journal of Labelled Compounds and Radiopharmaceuticals. Roč. 64, č. 2 (2021), s. 77-81. ISSN 0362-4803. E-ISSN 1099-1344
Institucionální podpora: RVO:61388963
Klíčová slova: GHB high-affinity binding sites * MCT1 uptake * radioligand binding * selective GHB ligand
Obor OECD: Analytical chemistry
Impakt faktor: 1.949, rok: 2021
Způsob publikování: Omezený přístup
https://doi.org/10.1002/jlcr.3870

GHB (γ‐hydroxybutyrate) is not only an endogenously present small molecule but also a clinically prescribed drug for the symptomatic treatment of narcolepsy. However, GHB's mechanism of action remains to be uncovered. Within the CNS, GHB targets both GABAB receptors and a pharmacologically distinct population of high‐affinity binding sites with unknown molecular identity. HOCPCA (3‐hydroxycyclopent‐1‐enecarboxylic acid) is a structural analog of GHB selectively targeting GHB high‐affinity binding sites. Here, we discuss the usefulness of 3H‐ and 11C‐labeled HOCPCA as radioligands for selectively probing GHB high‐affinity binding sites and their application in drug discovery. As such, [3H]HOCPCA's exceptional affinity and selectivity makes it an indispensable tool in drug discovery, and its utility has been demonstrated in, for example, homogenate binding studies, in vitro as well as ex vivo autoradiography. Moreover, the successful synthesis of [11C]HOCPCA is a starting point for further ligand development for future in vivo investigations of GHB high‐affinity binding sites.
Trvalý link: http://hdl.handle.net/11104/0318999