Highly Potent and Selective Dopamine D₄ Receptor Antagonists Potentially Useful for the Treatment of Glioblastoma.

ABSTRACT: To better understand the role of dopamine D₄ receptor (D₄R) in glioblastoma (GBM), in the present paper, new ligands endowed with high affinity and selectivity for D₄R were discovered starting from the brain penetrant and D₄R selective lead compound 1-(3-(4-phenylpiperazin-1-yl)propyl)-3,4-dihydroquinolin-2(1H)-one (6). In particular, the D₄R antagonist 24, showing the highest affinity and selectivity over D₂R and D₃R within the series (D₂/D₄ = 8318, D₃/D₄ = 3715), and the biased ligand 29, partially activating D₄R G_i-/G_o-protein and blocking β-arrestin recruitment, emerged as the most interesting compounds. Th

SUBMITTER: Pavletic P 

PROVIDER: S-EPMC9511495 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature