Pharmacophore modeling of diverse classes of p38 MAP kinase inhibitors

Mitogen-activated protein (MAP) p38 kinase is a serine–threonine protein kinase and its inhibitors are useful in the treatment of inflammatory diseases. Pharmacophore models were developed using HypoGen program of Catalyst with diverse classes of p38 MAP kinase inhibitors. The best pharmacophore hypothesis (Hypo1) with hydrogen-bond acceptor (HBA), hydrophobic (HY), hydrogen-bond donor (HBD), and ring aromatic (RA) as features has correlation coefficient of 0.959, root mean square deviation (RMSD) of 1.069 and configuration cost of 14.536. The model was validated using test set containing 119 compounds and had high correlation coefficient of 0.851. The results demonstrate that results obtained in this study can be considered to be useful and reliable tools in identifying structurally diverse compounds with desired biological activity.

Graphical abstractThe mitogen-activated protein (MAP) p38 kinase is a serine–threonine protein kinase and its inhibitors are useful in the treatment of inflammatory diseases. Pharmacophore models were developed using HypoGen program of Catalyst with a diverse classes of compounds containing 30 p38 MAP kinase inhibitors. The model was validated using test set containing 119 compounds and had a high correlation coefficient of 0.851.Figure optionsDownload full-size imageDownload as PowerPoint slide