Defining the Polycystin Pharmacophore Through HTS & Computational Biophysics.

ABSTRACT:

Background and purpose

Polycystins (PKD2, PKD2L1) are voltage-gated and Ca²⁺-modulated members of the transient receptor potential (TRP) family of ion channels. Loss of PKD2L1 expression results in seizure-susceptibility and autism-like features in mice, whereas variants in PKD2 cause autosomal dominant polycystic kidney disease. Despite decades of evidence clearly linking their dysfunction to human disease and demonstrating their physiological importance in the brain and kidneys, the polycystin pharmacophore remains undefined. Contributing to this knowledge gap is their resistance to drug screening campaigns, which are hindered by these channels' unique subcellular trafficking to organelles such as the primary cilium. PKD2L1 is the only member of the polycystin family t

SUBMITTER: Guadarrama E 

PROVIDER: S-EPMC11761769 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature