Conformationally restricted hydantoin-based peptidomimetics as inhibitors of caspase-3 with basic groups allowed at the S3 enzyme subsite

ChemMedChem. 2008 Jun;3(6):979-85. doi: 10.1002/cmdc.200800020.

Abstract

By using a combination of molecular modeling, combinatorial chemistry, and biological essays, novel scaffold molecules for the inhibition of caspase-3 have been developed. These compounds have an overall attenuated negative charge and show similar IC(50) values for both recombinant and human endogenous caspase-3. This might provide the basis for a novel strategy for the discovery of potent and more druglike inhibitors of caspase-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Binding Sites / drug effects
  • Caspase Inhibitors*
  • Cell Line
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Drug Evaluation, Preclinical
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydantoins / chemistry*
  • Molecular Conformation
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Recombinant Proteins / antagonists & inhibitors
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Hydantoins
  • Peptides
  • Recombinant Proteins