Discovery and optimisation of pyrazolo[1,5-a]pyrimidines as aryl hydrocarbon receptor antagonists.

ABSTRACT: The aryl hydrocarbon receptor (AHR) is a versatile ligand-dependent transcription factor involved in diverse biological processes, from metabolic adaptations to immune system regulation. Recognising its pivotal role in cancer immunology, AHR has become a promising target for cancer therapy. Here we report the discovery and structure-activity relationship studies of novel AHR antagonists. The potential AHR antagonists were identified via homology model-based high-throughput virtual screening and were experimentally verified in a luciferase reporter gene assay. The identified pyrazolo[1,5-a]pyrimidine-based AHR antagonist 7 (IC₅₀ = 650 nM) was systematically optimised to elucidate structure-activity relationships and reach low nanomolar AHR antagonistic potency (7a,

SUBMITTER: Bobrovs R 

PROVIDER: S-EPMC11376203 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature