3D-QSAR Modeling Studies on Pyrrolopyridinone Derivatives as Inhibitors of Cdc7 Kinase

The cell division cycle 7 (Cdc7) is a serine threonine kinase that is a key regulator of the S-phase of the cell cycle, known to promote the activation of DNA replication origins in eukaryotic organisms. Cdc7 has recently emerged as an attractive target for the development of novel Cdc7 small-molecule inhibitors for cancer treatment. In this paper, we have applied 3D-QSAR mod r2 eling to develop the structure-activity correlation of pyrrolopyridinone derivatives based on Cdc7 inhibitors. The study has resulted in two types of satisfactory 3D-QSAR models, including the CoMFA model (q2= 0.633, r2 = 0.871) and CoMSIA model (q2 = 0.587, r2 = 0.757), for predicting the biological activity of new compounds. The contour maps obtained from the 3D-QSAR models help to better interpret the structure-activity relationship. The satisfactory results suggest that the developed 3D-QSAR models are advisable to offer utility in predicting the activity and guiding the rational design of novel Cdc7 inhibitors with desired activity.