title: Recent Advances and New Strategies in Targeting Plk1 for Anticancer Therapy.
abstract: Polo-like kinase 1 (Plk1) plays key roles in regulating mitotic processes that are crucial for cellular proliferation. Overexpression of Plk1 is tightly associated with the development of particular cancers in humans, and a large body of evidence suggests that Plk1 is an attractive target for anticancer therapeutic development. Drugs targeting Plk1 can potentially be directed at two distinct sites: the N-terminal catalytic kinase domain (KD), which phosphorylates substrates, and the C-terminal polo-box domain (PBD) which is essential for protein-protein interactions. In this review we summarize recent advances and new challenges in the development of Plk1 inhibitors targeting these two domains. We also discuss novel strategies for designing and developing next-generation inhibitors to effectively treat Plk1-associated human disorders.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: kyunglee@mail.nih.gov.
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Terrence R
authors.initials: TR
authors.lastname: Burke
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute, 804-1, Yangcheong Ri, Ochang, Chungbuk, Cheongwon 363-883, Republic of Korea.
authors.forename: Jeong K
authors.initials: JK
authors.lastname: Bang
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Eunhye
authors.initials: E
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1