title: Omecamtiv mecarbil: a new cardiac myosin activator for the treatment of heart failure.
abstract: BACKGROUND
  Current available inotropic agents increase cardiac contractility, but are associated with myocardial ischemia, arrhythmias, and mortality. A novel selective cardiac myosin activator, omecamtiv mecarbil (CK-1827452/ AMG-423) is a small molecule that activates the sarcomere proteins directly, resulting in prolonged systolic ejection time and increased cardiac contractility.
  
  
  METHODS
  This paper discusses the chemistry, pharmacokinetics, clinical efficacy and safety of omecamtiv mecarbil. Omecamtiv mecarbil represents a novel therapeutic approach to directly improve cardiac function and is therefore proposed as a potential new treatment of patients with systolic heart failure. The authors review results of previous studies investigating the effect of omecamtiv mecarbil in heart failure animal models, healthy volunteers, and patients with acute and chronic systolic heart failure.
  
  
  CONCLUSIONS
  Results of phase I and phase II studies demonstrate that omecamtiv mecarbil is safe and well tolerated both as an intravenous and oral formulation. In healthy volunteers and chronic systolic heart failure patients, administration of omecamtiv mecarbil resulted in a concentration-dependent increase of left ventricular ejection time, ejection fraction, fractional shortening, and stroke volume. The first results of a double-blind, randomized, placebo-controlled phase IIb dose-finding study with the oral formulation of omecamtiv mecarbil demonstrated beneficial effects on cardiac function and N-terminal pro-brain natriuretic peptide levels. This study will provide essential dosing information for the requisite phase III trials which will investigate whether the beneficial effects of omecamtiv mecarbil translate into improved clinical outcomes.
authors.affiliation: a Department of Cardiology , University Medical Center Groningen, University of Groningen , Groningen , 9713 GZ , the Netherlands.
authors.forename: Licette Cy
authors.initials: LC
authors.lastname: Liu
authors.affiliation: a Department of Cardiology , University Medical Center Groningen, University of Groningen , Groningen , 9713 GZ , the Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Dorhout
authors.affiliation: a Department of Cardiology , University Medical Center Groningen, University of Groningen , Groningen , 9713 GZ , the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.affiliation: b Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine , University of California San Francisco , San Francisco , CA , USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.affiliation: a Department of Cardiology , University Medical Center Groningen, University of Groningen , Groningen , 9713 GZ , the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
mesh_terms: D000818:Animals; D024722:Cardiac Myosins / Q000187:drug effects* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic; D014508:Urea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; C547293:omecamtiv mecarbil; D014508:Urea; D024722:Cardiac Myosins
keywords: CK-1827452; cardiac myosin activator; heart failure with reduced ejection fraction; omecamtiv mecarbil