Compounds Designs of CK2α Inhibitors Derived from Virtual Screening Hit Compounds by Computational Chemistry with Crystallography

Chem Pharm Bull (Tokyo). 2024;72(9):776-780. doi: 10.1248/cpb.c23-00824.

Abstract

Protein kinase CK2 type α (CK2α) inhibitors are expected to be a new anticancer drug and a treatment for nephritis. Virtual screening for CK2α inhibitors has been conducted and active compounds with various scaffolds have been obtained. Research on compound optimization is currently in progress for some of them with the aim of improving their activity. This process involves the combination of various computational chemistry methods and crystal analyses. In this review, case studies of structure-based compound designs that have efficiently improved the activity of screening hit compounds, including compounds with a thiadiazole ring and a purine scaffold, are introduced.

Keywords: CK2α inhibitor; binding free energy; crystal water molecule; interaction entropy; protein kinase CK2; solvent dipole ordering-based virtual screening.

Publication types

  • Review

MeSH terms

  • Casein Kinase II* / antagonists & inhibitors
  • Casein Kinase II* / chemistry
  • Casein Kinase II* / metabolism
  • Computational Chemistry
  • Crystallography, X-Ray
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Structure
  • Protein Kinase Inhibitors* / chemistry
  • Protein Kinase Inhibitors* / pharmacology
  • Structure-Activity Relationship

Substances

  • Casein Kinase II
  • Protein Kinase Inhibitors