Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure

Bioorg Med Chem Lett. 1998 May 5;8(9):1019-22. doi: 10.1016/s0960-894x(98)00163-2.

Abstract

New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein kinases were investigated, and the compound (21) with Ac-Cys-Pro-Lys-Lys-NHMe connected with the triethylene glycol spacer exhibited the most potent inhibition with relatively high selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • CDC2 Protein Kinase / antagonists & inhibitors*
  • CDC2 Protein Kinase / chemistry
  • CDC2 Protein Kinase / metabolism
  • Catalytic Domain
  • Cyclin B / metabolism
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Histones / metabolism
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Models, Molecular
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Oligopeptides / pharmacology
  • Phosphorylation
  • Protein Kinase Inhibitors*
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Cyclin B
  • Enzyme Inhibitors
  • Histones
  • Indicators and Reagents
  • Oligopeptides
  • Protein Kinase Inhibitors
  • CDC2 Protein Kinase