Small-molecule therapies for cardiac hypertrophy: moving beneath the cell surface

Nat Rev Drug Discov. 2007 Aug;6(8):617-35. doi: 10.1038/nrd2193.

Abstract

Pathological stress from cardiovascular disease stimulates hypertrophy of heart cells, which increases the risk of cardiac morbidity and mortality. Recent evidence has indicated that inhibiting such hypertrophy could be beneficial, encouraging drug discovery and development efforts for agents that could achieve this goal. Most existing therapies that have antihypertrophic effects target outside-in signalling in cardiac cells, but their effectiveness seems limited, and so attention has recently turned to the potential of targeting intracellular signalling pathways. Here, we focus on new developments with small-molecule inhibitors of cardiac hypertrophy, summarizing both agents that have been in or are poised for clinical testing, and pathways that offer further promising potential therapeutic targets.

Publication types

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

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / chemistry
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
  • Amides / chemistry
  • Amides / therapeutic use
  • Animals
  • Cardiomegaly / drug therapy*
  • Cardiomegaly / metabolism
  • Cardiomegaly / physiopathology
  • Cardiovascular Agents / chemistry
  • Cardiovascular Agents / therapeutic use*
  • Humans
  • Models, Biological
  • Molecular Structure
  • Pyridines / chemistry
  • Pyridines / therapeutic use
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / physiology
  • Signal Transduction / drug effects

Substances

  • Amides
  • Cardiovascular Agents
  • Pyridines
  • Receptors, Cell Surface
  • Y 27632
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • fasudil