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

• Published in: European journal of medicinal chemistry 2015-05, Vol.96, p.396-404
• Main Authors: Nakanishi, Isao, Murata, Katsumi, Nagata, Naoya, Kurono, Masakuni, Kinoshita, Takayoshi, Yasue, Misato, Miyazaki, Takako, Takei, Yoshinori, Nakamura, Shinya, Sakurai, Atsushi, Iwamoto, Nobuko, Nishiwaki, Keiji, Nakaniwa, Tetsuko, Sekiguchi, Yusuke, Hirasawa, Akira, Tsujimoto, Gozoh, Kitaura, Kazuo
• Format: Article
• Language: English
• Subjects: Casein Kinase II - antagonists & inhibitors; Casein Kinase II - metabolism; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical - methods; Enzyme Activation - drug effects; Humans; In silico screening; Kinase inhibitor; Models, Molecular; Molecular similarity; Molecular Structure; Protein kinase CK2; Protein Kinase Inhibitors - analysis; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Solvent dipole ordering; Solvents - chemistry; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2015.04.032

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. [Display omitted] •Novel protein kinase CK2 inhibitors were identified using SDO virtual screening.•Identified compounds were categorized in 15 distinct scaffold classes.•Most of the identified compounds are lead-like and dissimilar to known inhibitors.•Crystal structures revealed the high accuracy of the predicted binding modes.