Targeting the insulin-regulated aminopeptidase/AT4 receptor for cognitive disorders

Drug News Perspect. 2009 Apr;22(3):133-9. doi: 10.1358/dnp.2009.22.3.1325032.

Abstract

The insulin-regulated aminopeptidase/AT(4) receptor has recently emerged as a new target for pharmaceutical agents aimed at treating various cognitive disorders such as Alzheimer's disease. There is an unmet need for metabolically stable drug-like angiotensin (Ang) IV analogues that exert actions mimicking the powerful memory-enhancing effects of Ang IV and LVV-hemorphin-7 and can efficiently cross the blood-brain barrier. Such new chemical entities would be attractive as research tools and would allow extensive study of the impact of Ang IV on in vivo physiology in complex animal models. Drug-like Ang IV peptidomimetics are foreseen to serve as potential lead structures for further optimization in drug discovery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / metabolism
  • Angiotensin II / pharmacology
  • Angiotensin II / therapeutic use
  • Angiotensin Receptor Antagonists*
  • Animals
  • Cognition Disorders / drug therapy*
  • Cystinyl Aminopeptidase / antagonists & inhibitors*
  • Drug Delivery Systems
  • Drug Discovery
  • Humans
  • Ligands
  • Models, Biological
  • Molecular Structure
  • Receptors, Angiotensin / agonists*

Substances

  • AT4 receptor
  • Angiotensin Receptor Antagonists
  • Ligands
  • Receptors, Angiotensin
  • Angiotensin II
  • angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-
  • Cystinyl Aminopeptidase
  • leucyl-cystinyl aminopeptidase