Abstract: ALK5 inhibitors,which can inhibit TGF- signaling pathway,play a vital role in medicine for treatment of many diseases,such as cancer,renal fibrosis and liver fibrosis.Herein,TGF- signaling inhibitors of 61 imidazole-based derivatives compounds for ALK5 were analyzed using common skeleton-based 3D-QSAR.We selected EW7197 as a template to generate common substructure-based alignmentsand further built both CoMFA and CoMSIA models.Through the values of r2 and q2 obtained,we may judge the merits of these models.The results indicate that the optimal CoMFA model has q2=0.716 and r2=0.905,the optimal CoMSIAmodel has q2=0.704 and r2=0.976.The outcomes of contour maps show that the hydrogen bond acceptor and hydrophobic features play key roles in models.Furthermore,the docking studies revealed important interactions between compounds and amino acids,and the obtained binding mode was in good agreement with the 3D-QSAR results.Based on our analysis and affirmation of docking simulations,we may lay a reliable theoretical foundation for designing new potential ALK5 inhibitors with higher activity and affinity.