Selective inhibitors of death in mutant huntingtin cells

Nat Chem Biol. 2007 Feb;3(2):99-100. doi: 10.1038/nchembio852. Epub 2006 Dec 31.

Abstract

Huntington disease (HD) is an inherited neurodegenerative disorder with unclear pathophysiology. We developed a high-throughput assay in a neuronal cell culture model of HD, screened 43,685 compounds and identified 29 novel selective inhibitors of cell death in mutant huntingtin-expressing cells. Four compounds were active in diverse HD models, which suggests a role for cell death in HD; these compounds are mechanistic probes and potential drug leads for HD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Caspase Inhibitors
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cell Line, Transformed
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Culture Media, Serum-Free / pharmacology
  • Drug Evaluation, Preclinical
  • Humans
  • Huntingtin Protein
  • Huntington Disease / drug therapy*
  • Huntington Disease / genetics
  • Molecular Structure
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nuclear Proteins / genetics*
  • Organic Chemicals / pharmacology*
  • PC12 Cells
  • Rats
  • Structure-Activity Relationship
  • Transfection

Substances

  • Caspase Inhibitors
  • Culture Media, Serum-Free
  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Organic Chemicals
  • Caspase 3

Associated data

  • PubChem-Substance/17424938
  • PubChem-Substance/17424939
  • PubChem-Substance/17424940
  • PubChem-Substance/17424941
  • PubChem-Substance/17424942
  • PubChem-Substance/17424943
  • PubChem-Substance/17424944
  • PubChem-Substance/17424945
  • PubChem-Substance/17424946
  • PubChem-Substance/17424947
  • PubChem-Substance/17424948
  • PubChem-Substance/17424949
  • PubChem-Substance/17424950
  • PubChem-Substance/17424951
  • PubChem-Substance/17424952
  • PubChem-Substance/17424953
  • PubChem-Substance/17424954
  • PubChem-Substance/17424955
  • PubChem-Substance/17424956
  • PubChem-Substance/17424957
  • PubChem-Substance/17424958
  • PubChem-Substance/17424959
  • PubChem-Substance/17424960
  • PubChem-Substance/17424961
  • PubChem-Substance/17424962
  • PubChem-Substance/17424963
  • PubChem-Substance/17424964
  • PubChem-Substance/17424965
  • PubChem-Substance/17424966
  • PubChem-Substance/17424967
  • PubChem-Substance/17424968
  • PubChem-Substance/17424969