title: Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1).
abstract: Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Nie
authors.forename: Victoria
authors.initials: V
authors.lastname: Feher
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Natala
authors.forename: Christopher
authors.initials: C
authors.lastname: McBride
authors.forename: Andre
authors.initials: A
authors.lastname: Kiryanov
authors.forename: Benjamin
authors.initials: B
authors.lastname: Jones
authors.forename: Betty
authors.initials: B
authors.lastname: Lam
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Stephen
authors.initials: S
authors.lastname: Kaldor
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stafford
authors.forename: Kouki
authors.initials: K
authors.lastname: Hikami
authors.forename: Noriko
authors.initials: N
authors.lastname: Uchiyama
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hikichi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Amano
authors.forename: Lilly
authors.initials: L
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Hosfield
authors.forename: Robert
authors.initials: R
authors.lastname: Skene
authors.forename: Hua
authors.initials: H
authors.lastname: Zou
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cao
authors.forename: Takashi
authors.initials: T
authors.lastname: Ichikawa
mesh_terms: D010129:4-Aminobenzoic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D001381:Azepines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D055808:Drug Discovery; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D055815:Young Adult; D000097869:Polo-Like Kinase 1
chemical_list: D010129:4-Aminobenzoic Acid; D001381:Azepines; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C573314:4-((9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido(4,5-b)(1,4)diazepin-2-yl)amino)-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide