Docking Study and Three‐Dimensional Quantitative Structure‐Activity Relationship (3D‐QSAR) Analyses of Transforming Growth Factor‐β Type I Receptor Kinase Inhibitors

Transforming growth factor‐β Type I Receptor Kinase (TGF‐β RI) is an important and novel drug target for the treatment of fibrosis and cancer. In this study, docking and comparative molecular field analysis (CoMFA) were performed and the structural characteristics of TGF‐β RI ligands were rationalized. The genetic algorithm search method in the docking program GOLD 3.0.1 was employed to determine the likely binding mode conformations of 70 inhibitors in the active site of TGF‐β RI. Based on the binding mode conformations, a highly predictive 3D‐QSAR model was developed with a q 2 value of 0.589 for CoMFA. The predictive ability of this model was validated with a number of compounds that were not included in the original training set. Furthermore, the 3D‐QSAR model was mapped back to the binding site of the TGF‐β RI to obtain a better understanding of the essential interactions between the inhibitors and TGF‐β RI. The robustness, predictive ability and automated alignment generation of this model make it a potential tool for the design and development of new drug leads to inhibit TGF‐β RI.