Physicochemical properties and biological efficacy of 30 DYRK2 Inhibitors for the treatment of prostate cancer

Prostate cancer is the most common cancer among men which has major diagnosis in the United States in 2017. Among DYRK class II members, dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) is the functional target for prostate cancer treatment. Studies show that subfamilies of DYRKs are also capable to phosphorylate (tyrosine, serine, and threonine) residues, yet little research has been carried out for its inhibitors. In this article, conceptual density theory is used to estimate the physicochemical properties of 30 experimentally synthesized inhibitors targeting DYRK2. The HOMO-LUMO gap showed low reactivity and high chemical activity for the inhibitors. The biological efficacy of these 30 inhibitors is predicted by bioavailability, mutagenicity, and cardiotoxicity measures. The inhibitors showed low toxicity and no blood brain barrier permeability. Results indicated that the physiological actions of these inhibitors involve multiple target interactions. Since the experimental results of the DYRK2 protein showed great water solubility, favorable safety properties, and potential anti-prostate cancer activities for ligand 24, docking and molecular dynamics simulations from the Galaxy webserver using Gromacs open-source tools are also performed for (DYRK2-24) complex (PDB: 7EJV). (DYRK2-24) showed strong binding affinity and noncovalent interactions. image