title: Multitarget cardiovascular drugs.
abstract: Cardiovascular disease is the number one cause of death globally. Design of cardiovascular drugs based on new paradigms is therefore a prominent goal of medicinal chemistry. Designed multiple ligands, targeting two or more proteins involved in pathogenesis of disease have become a viable concept in drug discovery. Although adjustment of the activities ratio at the different targets is a demanding and challenging task, modulation of two or more targets involved in a cardiovascular disease may be more successful for therapeutic application than treatment directed against each target alone, because of improved pharmacodynamic and pharmacokinetic properties of designed multitarget drugs. The article reviews the applications of multitarget approach to cardiovascular drug design, covering angiotensin-converting enzyme/neutral endopeptidase inhibitors, neutrale endopeptidase/endothelin-converting enzyme inhibitors, angiotensin-converting enzyme/neutral endopeptidase/endothelin-converting enzyme inhibitors, dual angiotensin/endothelin receptor and angiotensin1/angotensin2 receptor antagonists and angiotensin receptor antagonist/neutral endopeptidase inhibitors.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Slovenia.
authors.forename: U
authors.initials: U
authors.lastname: Trstenjak
authors.forename: D
authors.initials: D
authors.lastname: Kikelj
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D015195:Drug Design; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D045265:Natriuretic Peptides / Q000502:physiology; D015260:Neprilysin / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D016232:Endothelins; D004791:Enzyme Inhibitors; D045265:Natriuretic Peptides; D011480:Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D000072396:Endothelin-Converting Enzymes