title: Structure-based design of novel potent protein kinase CK2 (CK2) inhibitors with phenyl-azole scaffolds.
abstract: Protein kinase CK2 (CK2) is a ubiquitous serine/threonine protein kinase for hundreds of endogenous substrates. CK2 has been considered to be involved in many diseases, including cancers. Herein we report the discovery of a novel ATP-competitive CK2 inhibitor. Virtual screening of a compound library led to the identification of a hit 2-phenyl-1,3,4-thiadiazole compound. Subsequent structural optimization resulted in the identification of a promising 4-(thiazol-5-yl)benzoic acid derivative.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Zengye
authors.initials: Z
authors.lastname: Hou
authors.forename: Isao
authors.initials: I
authors.lastname: Nakanishi
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takei
authors.forename: Misato
authors.initials: M
authors.lastname: Yasue
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Misu
authors.forename: Yamato
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Shinya
authors.initials: S
authors.lastname: Nakamura
authors.forename: Tatsuhide
authors.initials: T
authors.lastname: Kure
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Katsumi
authors.initials: K
authors.lastname: Murata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitaura
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000266:Adenylyl Imidodiphosphate / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D013844:Thiazoles; D000266:Adenylyl Imidodiphosphate; D000255:Adenosine Triphosphate; D047390:Casein Kinase II