title: Structure-activity relationship study of 4-(thiazol-5-yl)benzoic acid derivatives as potent protein kinase CK2 inhibitors.
abstract: Two classes of modified analogs of 4-(thiazol-5-yl)benzoic acid-type CK2 inhibitors were designed. The azabenzene analogs, pyridine- and pyridazine-carboxylic acid derivatives, showed potent protein kinase CK2 inhibitory activities [IC50 (CK2α)=0.014-0.017μM; IC50 (CK2α')=0.0046-0.010μM]. Introduction of a 2-halo- or 2-methoxy-benzyloxy group at the 3-position of the benzoic acid moiety maintained the potent CK2 inhibitory activities [IC50 (CK2α)=0.014-0.016μM; IC50 (CK2α')=0.0088-0.014μM] and led to antiproliferative activities [CC50 (A549)=1.5-3.3μM] three to six times higher than those of the parent compound.
authors: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: hohno@pharm.kyoto-u.ac.jp.
authors: Hiroaki
authors: H
authors: Ohno
authors: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Daiki
authors: D
authors: Minamiguchi
authors: Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors: Shinya
authors: S
authors: Nakamura
authors: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Keito
authors: K
authors: Shu
authors: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Shiho
authors: S
authors: Okazaki
authors: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Maho
authors: M
authors: Honda
authors: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Ryosuke
authors: R
authors: Misu
authors: Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors: Hirotomo
authors: H
authors: Moriwaki
authors: Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors: Shinsuke
authors: S
authors: Nakanishi
authors: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Shinya
authors: S
authors: Oishi
authors: Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors: Takayoshi
authors: T
authors: Kinoshita
authors: Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors: Isao
authors: I
authors: Nakanishi
authors: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: nfujii@pharm.kyoto-u.ac.jp.
authors: Nobutaka
authors: N
authors: Fujii
mesh_terms: D019817:Benzoic Acid / Q000737:chemistry* / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D013844:Thiazoles; D019817:Benzoic Acid; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II
keywords: Kinase inhibitor; Protein kinase CK2; Rational design; Structure–activity relationship