Targeting the substrate binding domain of polo-like kinase 1: advances in the study of PBD1 inhibitors.
- Author:
Liang ZHANG
1
;
Yan-Hua CAO
;
Shuai LU
;
Shan-Liang SUN
;
Hai-Chun LIU
;
Tao LU
Author Information
1. Department of Organic Chemistry, China Pharmaceutical University, Nanjing 210009, China.
- Publication Type:Journal Article
- MeSH:
Benzocycloheptenes;
chemistry;
pharmacology;
Benzoquinones;
chemistry;
pharmacology;
Cell Cycle Proteins;
antagonists & inhibitors;
chemistry;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Humans;
Indole Alkaloids;
chemistry;
pharmacology;
Lactams;
chemistry;
pharmacology;
Peptides, Cyclic;
chemistry;
pharmacology;
Phosphopeptides;
chemistry;
pharmacology;
Protein-Serine-Threonine Kinases;
antagonists & inhibitors;
chemistry;
Proto-Oncogene Proteins;
antagonists & inhibitors;
chemistry
- From:
Acta Pharmaceutica Sinica
2013;48(3):315-324
- CountryChina
- Language:Chinese
-
Abstract:
Polo-box domain 1 (PBD1) is a characteristic domain of polo-like kinase 1 (PLK1), which locates in C-terminal and can influence the catalytic activity and specific subcellular locations of PLK1. At present, most PLK1 inhibitors are developed to occupy the ATP pocket or its close sites. However, this kind of PLK1 inhibitors is difficult to pursue target selectivity and may encounter cross drug resistance with other kinase inhibitors due to the conserved sequence of ATP pocket. Recently, PBD1, with aberrant specificity in sequence and structure, has attracted enormous interests as the alternative target to the discovery of corresponding inhibitors for anti-tumor drugs. The structure and function of PBD1 as well as the advances of its inhibitors are reviewed in this paper.
