Identification of protein kinase CK2 inhibitors using solvent dipole ordering virtual screening

  • Eur J Med Chem. 2015;96:396-404. doi: 10.1016/j.ejmech.2015.04.032.
Isao Nakanishi  1 ,  Katsumi Murata  2 ,  Naoya Nagata  2 ,  Masakuni Kurono  2 ,  Takayoshi Kinoshita  3 ,  Misato Yasue  2 ,  Takako Miyazaki  2 ,  Yoshinori Takei  2 ,  Shinya Nakamura  4 ,  Atsushi Sakurai  4 ,  Nobuko Iwamoto  4 ,  Keiji Nishiwaki  4 ,  Tetsuko Nakaniwa  3 ,  Yusuke Sekiguchi  3 ,  Akira Hirasawa  2 ,  Gozoh Tsujimoto  2 ,  Kazuo Kitaura  2
Affiliations
  • 1. 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: [email protected].
  • 2. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • 3. Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
  • 4. Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
PMID: 25912672 DOI: 10.1016/j.ejmech.2015.04.032
Abstract

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.

Keywords
In silico screening; Kinase inhibitor; Molecular similarity; Protein kinase CK2; Solvent dipole ordering.
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