Therapeutic targeting of the angiotensin-converting enzyme 2/Angiotensin-(1-7)/Mas cascade in the renin-angiotensin system: a patent review

Expert Opin Ther Pat. 2012 May;22(5):567-74. doi: 10.1517/13543776.2012.682572. Epub 2012 Apr 18.


Introduction: The renin-angiotensin system (RAS) is a main therapeutic target for cardiovascular diseases. Within the last two decades, novel components of the RAS have been discovered, opening new opportunities to interfere with its activity. Angiotensin(Ang)-(1-7) is synthesized by angiotensin-converting enzyme 2 (ACE2), and interacts with the G-protein-coupled receptor Mas. The axis formed by ACE2/Ang-(1-7)/Mas represents an endogenous counter regulatory pathway within the RAS.

Areas covered: In this review, the authors discuss patents and recent initiatives to develop therapeutic strategies based on the ACE2/Ang-(1-7)/Mas axis.

Expert opinion: Many publications and patents support a strategy to interfere with the activity of the RAS by stimulating its counter-regulatory axis mainly in two different ways: i) To increase the activity of ACE2, which will impact the system by increasing the inactivation of Ang II and the production of Ang-(1-7); ii) To stimulate Mas, taking advantage of nanostructured formulations of the natural peptide or analogues of Ang-(1-7). Although the preclinical studies are compelling, the possible impact of these novel therapeutic tools for the treatment of cardiometabolic diseases will only be known after completion of the ongoing clinical studies.

Publication types

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

MeSH terms

  • Angiotensin I / chemistry
  • Angiotensin I / metabolism
  • Angiotensin I / pharmacology*
  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Cardiovascular Agents / chemistry
  • Cardiovascular Agents / pharmacology*
  • Drug Design
  • Enzyme Activation
  • Enzyme Activators / chemistry
  • Enzyme Activators / pharmacology*
  • Humans
  • Legislation, Drug
  • Molecular Structure
  • Patents as Topic
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Peptidyl-Dipeptidase A / metabolism
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / agonists*
  • Proto-Oncogene Proteins / metabolism
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Renin-Angiotensin System / drug effects*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship


  • Cardiovascular Agents
  • Enzyme Activators
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Angiotensin II
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)