Exploiting polarity and chirality to probe the Hsp90 C-terminus

Bioorg Med Chem. 2018 Jul 23;26(12):3096-3110. doi: 10.1016/j.bmc.2018.04.028. Epub 2018 Apr 13.

Abstract

Inhibition of the Hsp90 C-terminus is an attractive therapeutic approach for the treatment of cancer. Novobiocin, the first Hsp90 C-terminal inhibitor identified, contains a synthetically complex noviose sugar that has limited the generation of structure-activity relationships for this region of the molecule. The work described herein utilizes various ring systems as noviose surrogates to explore the size and nature of the surrounding binding pocket.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclohexanols / chemical synthesis
  • Cyclohexanols / chemistry
  • Cyclohexanols / pharmacology
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • MCF-7 Cells
  • Novobiocin / chemical synthesis
  • Novobiocin / chemistry
  • Novobiocin / pharmacology
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Protein Domains
  • Structure-Activity Relationship

Substances

  • Biphenyl Compounds
  • Cyclohexanols
  • HSP90 Heat-Shock Proteins
  • Piperidines
  • Novobiocin
  • phenylcyclohexane