Identification of protein kinase CK2 inhibitors using solvent dipole ordering virtual screening.
Novel protein kinase CK2 inhibitors were identified using the solvent dipole ordering virtual screening method. A total of 26 compounds categorized in 15 distinct scaffold classes inhibited greater than 50% of enzyme activity at 50 μM, and eight exhibited IC50 values less than 10 μM. Most of the identified compounds are lead-like and dissimilar to known inhibitors. The crystal structures of two of the CK2 complexes revealed the high accuracy of the predicted binding modes.
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan. Electronic address: isayan@phar.kindai.ac.jp.
Isao
I
Nakanishi
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Katsumi
K
Murata
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Naoya
N
Nagata
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Masakuni
M
Kurono
Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Takayoshi
T
Kinoshita
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Misato
M
Yasue
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Takako
T
Miyazaki
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Yoshinori
Y
Takei
Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Shinya
S
Nakamura
Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Atsushi
A
Sakurai
Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Nobuko
N
Iwamoto
Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Keiji
K
Nishiwaki
Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Tetsuko
T
Nakaniwa
Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Yusuke
Y
Sekiguchi
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Akira
A
Hirasawa
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Gozoh
G
Tsujimoto
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Kazuo
K
Kitaura
D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D012997:Solvents; D047390:Casein Kinase II
In silico screening; Kinase inhibitor; Molecular similarity; Protein kinase CK2; Solvent dipole ordering