Pharmaceuticals, Год журнала: 2025, Номер 18(5), С. 741 - 741

Опубликована: Май 17, 2025

Background: Casein kinase 1 epsilon (CK1ε) plays a critical role in cancer progression by activating oncogenic signaling pathways, making it target for therapy. However, no inhibitors are currently available clinical use, highlighting the need novel therapeutic candidates. Methods: This study aimed to identify potential CK1ε inhibitors. To achieve this, modified version of previously reported pharmacophore model was applied an ultra-large database over 100 million compounds virtual screening. Hits were filtered based on drug-likeness and pH-dependent compliance then grouped according their structural core. A representative compound from each group underwent molecular dynamic (MD) simulations binding free energy calculations predict its stability affinity, allowing extrapolation results entire set Results: Pharmacophore matching initially identified 290 compounds. After minimization, assessment compliance, we selected 29 structurally related MD showed that most groups had stable modes, favorable intermolecular interactions, energies comparable those An analysis additional members promising two 2,4-diaminopyrimidine-based likely inhibit CK1ε. Conclusions: These findings provide insights into design inhibitors, supporting optimization eventual development targeted therapeutics.

Язык: Английский