Virtual Compound Screening for Discovery of Dopamine D1 Receptor Biased Allosteric Modulators.

ABSTRACT: The dopamine D1 receptor (D1R) is a therapeutic target for a variety of central nervous system disorders including Parkinson's disease (PD). Challenges thus arise in the development of safer D1R therapies in limiting off-target drug activity. This issue is particularly relevant to PD therapy, where L-DOPA has been the "gold standard" drug for decades despite a problematic side-effect profile. Recent studies of G-protein and β-arrestin functionally selective signaling offer new strategies for developing superior D1R orthosteric and allosteric compounds with fewer side effects. We designed a desktop-computer drug-screening platform to examine large virtual chemical libraries for allosteric compounds binding D1R intracellular loop 2 (ICL2) determinants. Two structurally distinct hits were str

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12478865 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature