Discovery and synthesis of the first selective BAG domain modulator of BAG3 as an attractive candidate for the development of a new class of chemotherapeutics

Chem Commun (Camb). 2018 Jul 5;54(55):7613-7616. doi: 10.1039/c8cc03399d.

Abstract

BAG3 protein has emerged as a key regulator of important cellular processes and its expression is increased in some tumor types; however, despite its potential value for future chemotherapeutics, no selective BAG3 modulators have been yet reported. Here we report the 2,4-thiazolidinedione derivative 28 as the first BAG3 protein modulator.

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors*
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis Regulatory Proteins / antagonists & inhibitors*
  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Line, Tumor
  • HSP70 Heat-Shock Proteins / antagonists & inhibitors
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Multimerization / drug effects
  • Thiazolidinediones / chemical synthesis
  • Thiazolidinediones / chemistry
  • Thiazolidinediones / metabolism*
  • Thiazolidinediones / pharmacology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BAG3 protein, human
  • HSP70 Heat-Shock Proteins
  • Thiazolidinediones