title: Small-molecule therapies for cardiac hypertrophy: moving beneath the cell surface.
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.
authors.affiliation: Gilead Colorado, Inc., 7575 West 103rd Avenue, Westminster, Colorado 80021, USA. timothy.mckinsey@gilead.com
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McKinsey
authors.forename: David A
authors.initials: DA
authors.lastname: Kass
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use; D000577:Amides / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000577:Amides; D002317:Cardiovascular Agents; D011725:Pyridines; D011956:Receptors, Cell Surface; C108830:Y 27632; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil