Discovery and Characterization of Novel FGFR1 V561M Inhibitors via Virtual Screening and Molecular Dynamics Simulations.

The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive virtual screening protocol that combines energy-based screening and machine learning techniques, leading to the identification of a novel compound, . This compound exhibited potent inhibitory activity against FGFR1 V561M with an IC of 90.

Discovery of a ubiquitin-specific protease 10 inhibitor with high binding affinity promoting cell apoptosis via down-regulated CDK4 for the treatment of hepatocellular carcinoma.

Ubiquitin-specific protease 10 (USP10) has been associated with unfavorable prognoses in hepatocellular carcinoma (HCC) and represents a promising therapeutic target. However, current USP10 inhibitors demonstrate limited binding affinity and efficacy, highlighting the urgent need for novel compounds. This study builds upon the previously identified USP10 inhibitor D1 and introduces compound LY-2, which exhibits significantly enhanced binding affinity compared to D1, thereby establishing it as a promising candidate through comprehensive structure-activity relationship (SAR) analysis.