Defining the polycystin pharmacophore through high-throughput screening and computational biophysics.

ABSTRACT:

Background and purpose

Polycystins (PKD2, PKD2L1) are voltage-gated and Ca²⁺-modulated members of the TRP family of ion channels. Loss of PKD2L1 results in seizure-susceptibility and autism-like features in mice, whereas variants in PKD2 cause autosomal dominant polycystic kidney disease. Despite decades of evidence demonstrating their physiological importance in the brain and kidneys and linking their dysfunction to human disease, the polycystin pharmacophore remains undefined. Contributing to this knowledge gap is their resistance to drug screening campaigns, which are hindered by the unique subcellular trafficking of these channels to organelles such as the primary cilium. PKD2L1 is the only member of the polycystin family to form constitutively active ion channels in

SUBMITTER: Guadarrama E 

PROVIDER: S-EPMC12862858 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature