title: Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding.
abstract: A series of thiophene PLK1 inhibitors was optimized for increased solubility and reduced protein binding through the appendage of basic amine functionality. Interesting selectivity between PLK1 and PLK3 was also obtained through these modifications.
authors.affiliation: Five Moore Drive, Research Triangle Park, NC 27709, GlaxoSmithKline, USA.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Emmitte
authors.forename: George M
authors.initials: GM
authors.lastname: Adjabeng
authors.forename: George M
authors.initials: GM
authors.lastname: Adjebang
authors.forename: C Webb
authors.initials: CW
authors.lastname: Andrews
authors.forename: Jennifer G Badiang
authors.initials: JG
authors.lastname: Alberti
authors.forename: Ramesh
authors.initials: R
authors.lastname: Bambal
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Chamberlain
authors.forename: Ronda G
authors.initials: RG
authors.lastname: Davis-Ward
authors.forename: Hamilton D
authors.initials: HD
authors.lastname: Dickson
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hassler
authors.forename: Keith R
authors.initials: KR
authors.lastname: Hornberger
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Jackson
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Kuntz
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Lansing
authors.forename: Robert A
authors.initials: RA
authors.lastname: Mook
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Nailor
authors.forename: Mark A
authors.initials: MA
authors.lastname: Pobanz
authors.forename: Stephon C
authors.initials: SC
authors.lastname: Smith
authors.forename: Chiu-Mei
authors.initials: CM
authors.lastname: Sung
authors.forename: Mui
authors.initials: M
authors.lastname: Cheung
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008938:Mitosis; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012995:Solubility; D013876:Thiophenes / Q000737:chemistry*; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; D000097868:Polo-like Kinases
chemical_list: D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D013876:Thiophenes; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C486256:PLK3 protein, human; D000097868:Polo-like Kinases