Drug Repurposing by Virtual Screening: Identification of New Already Approved ROCK Inhibitors as Promising Drugs to Target Neurodegeneration.

ABSTRACT: ROCK kinases are key players in neurodegenerative diseases such as Alzheimer's disease (AD), making them attractive therapeutic targets. In this study, we developed a pharmacophoric map of ROCK inhibitors and highlighted the key affinity sites in ROCK1/2 through molecular modeling. Virtual screening led to the identification of six approved drugs as ROCK inhibitors: ruxolitinib (36), baricitinib (37), ponatinib (38), tivozanib (39), nialamide (40), and tucatinib (41). Ruxolitinib (36) (hROCK1 IC₅₀ = 0.025 μM; hROCK2 IC₅₀ = 0.007 μM) and baricitinib (37) (hROCK1 IC₅₀ = 0.019 μM; hROCK2 IC₅₀ = 0.011 μM) showed the highest potency, while tivozanib (39) display

SUBMITTER: Silva Franco L 

PROVIDER: S-EPMC12242638 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature