Targeting the Hsp90 C-terminal domain by the chemically accessible dihydropyrimidinone scaffold

Chem Commun (Camb). 2015 Mar 4;51(18):3850-3. doi: 10.1039/c4cc10074c.

Abstract

Hsp90 C-terminal ligands are potential new anti-cancer drugs alternative to the more studied N-terminal inhibitors. Here we report the identification of a new dihydropyrimidinone binding the C-terminus, which is not structurally related to other well-known natural and nature-inspired inhibitors of this second druggable Hsp90 site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Binding Sites
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Ligands
  • Protein Structure, Tertiary
  • Pyrimidinones / chemistry
  • Pyrimidinones / pharmacology*

Substances

  • Antineoplastic Agents
  • HSP90 Heat-Shock Proteins
  • Ligands
  • Pyrimidinones