title: Therapeutic targeting of the angiotensin-converting enzyme 2/Angiotensin-(1-7)/Mas cascade in the renin-angiotensin system: a patent review.
abstract: BACKGROUND
  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.
  
  
  METHODS
  In this review, the authors discuss patents and recent initiatives to develop therapeutic strategies based on the ACE2/Ang-(1-7)/Mas axis.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Federal University of Minas Gerais, Biological Sciences Institute, Department of Morphology, Belo Horizonte, MG, 31.270-901, Brazil.
authors.forename: Anderson J
authors.initials: AJ
authors.lastname: Ferreira
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
mesh_terms: D000803:Angiotensin I / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002317:Cardiovascular Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007880:Legislation, Drug; D015394:Molecular Structure; D010330:Patents as Topic; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D002317:Cardiovascular Agents; D020536:Enzyme Activators; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)