Molecular docking, molecular dynamics simulations and screening reveal cefixime and ceftriaxone as GSK3β covalent inhibitors.

GSK3β is a serine/threonine kinase that has been suggested as a putative drug target for several diseases. Recent studies have reported the beneficial effects of cephalosporin antibiotics in cancer and Alzheimer's disease, implying potential inhibition of GSK3β. To investigate this mechanism, four cephalosporins, namely, cefixime, ceftriaxone, cephalexin and cefadroxil were docked into the GSK3β binding pocket.

Discovery of new Cdc2-like kinase 4 (CLK4) inhibitors pharmacophore exploration combined with flexible docking-based ligand/receptor contact fingerprints and machine learning.

Cdc2-like kinase 4 (CLK4) inhibitors are of potential therapeutic value in many diseases particularly cancer. In this study, we combined extensive ligand-based pharmacophore exploration, ligand-receptor contact fingerprints generated by flexible docking, physicochemical descriptors and machine learning-quantitative structure-activity relationship (ML-QSAR) analysis to investigate the pharmacophoric/binding requirements for potent CLK4 antagonists. Several ML methods were attempted to tie these properties with anti-CLK4 bioactivities including multiple linear regression (MLR), random forests (RF), extreme gradient boosting (XGBoost), probabilistic neural network (PNN), and support vector regression (SVR).