Design, Synthesis, and Biological Evaluation of 3,4-Dihydroisoquinolin-1()-one Derivatives as Protein Arginine Methyltransferase 5 Inhibitors for the Treatment of Non-Hodgkin's Lymphoma.

Through catalyzing the transfer of methyl groups onto the guanidinium of arginine, protein arginine methyltransferase 5 (PRMT5) was essential to the cell growth of cancer cells. By utilizing a scaffold hopping strategy, a novel series of 3,4-dihydroisoquinolin-1()-one derivatives were designed and synthesized. Through a systematic SAR study, demonstrated excellent PRMT5 inhibitory activity, potent antiproliferative activity against Z-138, favorable pharmacokinetic profiles, and low hERG toxicity.

Kinase-Bench: Comprehensive Benchmarking Tools and Guidance for Achieving Selectivity in Kinase Drug Discovery.

Developing selective kinase inhibitors remains a formidable challenge in drug discovery because of the highly conserved structural information on adenosine triphosphate (ATP) binding sites across the kinase family. Tailoring docking protocols to identify promising kinase inhibitor candidates for optimization has long been a substantial obstacle to drug discovery. Therefore, we introduced "Kinase-Bench," a pioneering benchmark suite designed for an advanced virtual screen, to improve the selectivity and efficacy of kinase inhibitors.

Design, Synthesis, and Biological Activities Evaluation of Type I FLT3 Inhibitors for the Treatment of Acute Myeloid Leukemia.

The abnormal overexpression of FLT3 kinase is intimately associated with pathogenesis of acute myeloid leukemia (AML), positioning FLT3 inhibitors as pivotal therapeutic agents. Despite the availability of three FDA-approved FLT3 inhibitors, their clinical utility is hampered by resistance stemming from tyrosine kinase domain (TKD) mutations. Through an integrative analysis of case studies, we identified a potential advantage of type I FLT3 inhibitors in overcoming TKD mutation-induced resistance.

Global gene expression analysis in liver of db/db mice treated with catalpol.

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control.