ABSTRACT Polo‐like kinase 4 (PLK4) is a centrosome‐specific kinase aberrantly expressed in cancers. Drugs inhibiting its catalytic kinase domain are under clinical phase‐1/2 trials in patients with different leukemia types. However, the kinase domain of PLK4 shows structural similarity with other kinases. Therefore, drugs targeting the unique C‐terminal polo‐box domain (PBD) of PLK4 could provide better specificity. The knowledge of domain orientation in a full‐length PLK4 structure is imperative for drug discovery. In this work, we utilized ab initio and threading approaches to predict the full‐length structure of human PLK4, which was employed for virtually screening the ChEMBL library. Among the hit compounds targeting the unique regions in PLK4, we identified Alectinib, which affects centrosome numbers corresponding to PLK4 levels at centrosomes. The FT‐IR analysis also confirmed Alectinib interaction with the PBD. Therefore, this work identifies a chemical scaffold that could be repurposed to target the unique regions of PLK4.