Title:Discovery of Polo-like Kinase 4 Inhibitors for the Treatment of Cancer:
A Mini Patent Review
Volume: 23
Issue: 1
Author(s): Yang Shu, Yajing Liu, Shirong Bian, Zhouling Xie*Chenzhong Liao*
Affiliation:
- Department of Pharmaceutical Sciences and Engineering, School of Food and Biological Engineering, Hefei University
of Technology, Hefei, 230009, P.R. China
- Department of Pharmaceutical Sciences and Engineering, School of Food and Biological Engineering, Hefei University
of Technology, Hefei, 230009, P.R. China
Keywords:
Polo-like kinases, PLK4, centrosome amplification, cancer, inhibitor, patent.
Abstract: Polo-like kinase 4 (PLK4), a serine/threonine kinase, is a member of the PLK family.
As a key regulator of the cell cycle, PLK4 controls centrosome duplication and mitosis. Abnormal
PLK4’s function can induce centrosome amplification, leading to tumorigenesis, therefore, PLK4
has been regarded as a promising target for cancer therapy, and PLK4 inhibitors have potentials to
treat multiple cancers and other PLK4-associated human disorders, such as myelodysplastic syndrome.
In addition, PLK4 may function as a DNA-damage sensitizer, therefore improving the
efficacy of chemotherapy. To date, some small-molecule inhibitors with different chemical scaffolds
targeting PLK4 have been reported, among which, CFI-400945 has entered clinical trials for
the treatment of various solid tumors, myeloid leukemia, and myelodysplastic syndrome. In this
review, the structure and biological functions of PLK4 with other homologous PLKs are compared;
the roles of PLK4 in different cancers are reviewed; and PLK4 inhibitors disclosed in patent
or literature are summarized. Used alone or in combination with other anticancer drugs in
preclinical and clinical studies, PLK4 inhibitors have shown significant efficacy in the treatment
of different cancers, demonstrating that PLK4 could be a critical target for cancer diagnosis and
therapy. However, our understanding of PLK4 is still limited, and novel mechanisms of PLK4
should be identified in future studies.
