title: Developments of polo-like kinase 1 (Plk1) inhibitors as anti-cancer agents.
abstract: Polo-like kinases (Plks) are a family of serine/threonine kinases with a highly conserved N-terminal Ser/Thr kinase catalytic domain and a C-terminal region that play crucial roles in cell cycle progression. Plk1, playing a key role in multiple steps of mitotic progression, is the most studied member of the family. It is overexpressed in a wide spectrum of cancer types and is a promising target in oncology. Most of Plk1 inhibitors competitively bind to the ATP-binding site, which is characterized with unique features. Other inhibitors target regions outside the ATP pocket. In this review some pre-clinical or clinical Plk1 inhibitors are reported, focusing on SAR studies and biological activities, including the kinase activity, in vitro and in vivo anti-tumor efficacy. Those studies exhibited the inhibitors' significant therapeutic effects. Moreover, combination therapies of these Plk1 inhibitors with other anticancer drugs resulted with synergistic effects.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong, 250012, China. xuwenf@sdu.edu.cn.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001570:Benzodiazepinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; D001570:Benzodiazepinones; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D000097869:Polo-Like Kinase 1