PK 11195 derivatives: exploring the influence of amide and heterocyclic substitution on A147T TSPO discrimination.

ABSTRACT: The translocator protein (TSPO) is an 18 kDa protein on the outer mitochondrial membrane. It has gained significant interest in recent years for its potential as a therapeutic target and imaging biomarker, particularly in neuroinflammation, cancer, and central nervous system disorders (CNS). Clinical translation of ligands has been complicated by the presence of a common single nucleotide polymorphism (A147T TSPO), at which many disclosed TSPO ligands lose affinity. One exception is the first-generation TSPO ligand PK 11195, however, this ligand possesses unfavourable pharmacokinetic properties limiting translation in CNS applications. We aimed to investigate which motifs of this ligand contribute to high binding at the wild type (WT) and A147T TSPO isoforms with the aim of identifying ele

SUBMITTER: Sokias R 

PROVIDER: S-EPMC11883422 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature