Identification of drug repurposing candidates for the treatment of polycystic kidney disease - PubMed
3 hours ago
- #polycystic kidney disease
- #drug repurposing
- #target identification
- Three drug repurposing candidates—birinapant, bardoxolone methyl, and salicylic acid—were identified for treating autosomal dominant polycystic kidney disease (ADPKD).
- Shared effects among the drugs included thermal shifts in ADP/ATP translocases (SLC25A4/5/6) due to reduced ATP production.
- Salicylic acid demonstrated a polypharmacological profile, targeting enzymes in the N-linked glycosylation pathway and inhibiting PTK2 (FAK), a key activator of the PI3K/Akt/mTOR pathway linked to cyst growth.
- Computational modelling confirmed the binding site of salicylic acid (residues 499-504) within PTK2's ATP-binding pocket, with engagement of several targets at clinically relevant concentrations.
- Salicylic acid, the metabolite of aspirin, was highlighted as the most promising repurposing candidate due to its multifaceted mechanisms of action in preclinical models of ADPKD.