title: Discovery of a potent and selective aurora kinase inhibitor.
abstract: This communication describes the discovery of a novel series of Aurora kinase inhibitors. Key SAR and critical binding elements are discussed. Some of the more advanced analogues potently inhibit cellular proliferation and induce phenotypes consistent with Aurora kinase inhibition. In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models.
authors.affiliation: Medicinal Chemistry, Sunesis Pharmaceuticals, 395 Oyster Point Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Johan D
authors.initials: JD
authors.lastname: Oslob
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Romanowski
authors.forename: Darin A
authors.initials: DA
authors.lastname: Allen
authors.forename: Subramanian
authors.initials: S
authors.lastname: Baskaran
authors.forename: Minna
authors.initials: M
authors.lastname: Bui
authors.forename: Robert A
authors.initials: RA
authors.lastname: Elling
authors.forename: William M
authors.initials: WM
authors.lastname: Flanagan
authors.forename: Amy D
authors.initials: AD
authors.lastname: Fung
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Hanan
authors.forename: Shannon
authors.initials: S
authors.lastname: Harris
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Heumann
authors.forename: Ute
authors.initials: U
authors.lastname: Hoch
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Jacobs
authors.forename: Joni
authors.initials: J
authors.lastname: Lam
authors.forename: Chris E
authors.initials: CE
authors.lastname: Lawrence
authors.forename: Robert S
authors.initials: RS
authors.lastname: McDowell
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Nannini
authors.forename: Wang
authors.initials: W
authors.lastname: Shen
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Silverman
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Sopko
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Tangonan
authors.forename: Juli
authors.initials: J
authors.lastname: Teague
authors.forename: Josh C
authors.initials: JC
authors.lastname: Yoburn
authors.forename: Chul H
authors.initials: CH
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Zimmerman
authors.forename: Tom
authors.initials: T
authors.lastname: O'Brien
authors.forename: Willard
authors.initials: W
authors.lastname: Lew
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D064127:Aurora Kinases; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000201:enzymology; D010671:Phenylurea Compounds / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C532454:SNS 314; D013844:Thiazoles; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases