Discovery and SAR of thiazolidine-2,4-dione analogues as insulin-like growth factor-1 receptor (IGF-1R) inhibitors via hierarchical virtual screening

J Med Chem. 2010 Mar 25;53(6):2661-5. doi: 10.1021/jm901798e.

Abstract

Insulin-like growth factor-1 receptor (IGF-1R) is a growth factor receptor tyrosine kinase acting as a critical mediator of cell proliferation and survival. Novel 5-benzylidenethiazolidine-2,4-dione (5) and 5-(furan-2-ylmethylene)thiazolidine-2,4-dione (6) compounds were identified as potent and selective IGF-1R inhibitors via hierarchical virtual screening. Initial SAR and biological activity of the analogues of 5 and 6 with thiazolidine-2,4-dione template are presented, and several inhibitors with low nanomolar potency are reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Discovery / methods*
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Structure, Tertiary
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / chemistry
  • Receptor, IGF Type 1 / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thiazolidinediones / chemistry
  • Thiazolidinediones / metabolism
  • Thiazolidinediones / pharmacology*

Substances

  • Protein Kinase Inhibitors
  • Thiazolidinediones
  • thiazolidine-2,4-dione
  • Receptor, IGF Type 1