WaterMap and Molecular Dynamic Simulation-Guided Discovery of Potential PAK1 Inhibitors Using Repurposing Approaches.

ABSTRACT: p21-Activated kinase 1 (PAK1) is positioned at the nexus of several oncogenic signaling pathways. Currently, there are no approved inhibitors for disabling the transfer of phosphate in the active site directly, as they are limited by lower affinity, and poor kinase selectivity. In this work, a repurposing study utilizing FDA-approved drugs from the DrugBank database was pursued with an initial selection of 27 molecules out of ∼2162 drug molecules, based on their docking energies and molecular interaction patterns. From the molecules that were considered for WaterMap analysis, seven molecules, namely, Mitoxantrone, Labetalol, Acalabrutinib, Sacubitril, Flubendazole, Trazodone, and Niraparib, ascertained the ability to overlap with high-energy hydration sites. Considering many other displace

SUBMITTER: Biswal J 

PROVIDER: S-EPMC8529594 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature