Ensemble docking-based virtual screening toward identifying inhibitors against Wee1 kinase.

kinase plays a key role in the arrest of G2/M checkpoint that prevents mitotic entry in response to DNA damage. This work is to discover potent Wee1 inhibitors which can be considered valuable. Herein, Ensemble docking using multiple crystal structures was considered an effective strategy in the virtual screening. The performance of 17 scoring functions obtained from different docking software was evaluated for molecular docking. Two novel compounds B1 and A2 were identified as Wee1 inhibitors with IC values of 10.23 ± 0.505 and 8.72 ± 0.323 μM, respectively. Further cell viability assay demonstrated that the two active compounds exhibited good anticancer activities. This provides a meaningful starting point for further structure optimization to discover more potent Wee1 inhibitors.