Novel drug targets in clinical development for heart failure.
BACKGROUND
Heart Failure continues to be a leading cause of mortality and morbidity worldwide. The dismal prognosis of patients in acute heart failure (AHF) can be altered only by exploring novel drug molecules. Although the treatment for chronic heart failure (CHF) has seen remarkable progress, there is still a need to develop molecules that could improve the long-term survival outcomes.


OBJECTIVE
To review the drug targets for acute and chronic heart failure and the molecules acting on these targets.


METHODS
The article discusses on the mechanism of how the potential drug targets can be modulated to alter the pathophysiological processes in heart failure. Current evidence on molecules acting on these targets has also been described from published literature using the PubMed and Clinical Trials.gov databases.


RESULTS
Some of the molecules that are currently being explored for AHF includeomecamtiv mecarbil which activates cardiac myosin ATPase, istaroxime an ionotropicagent that activates SERCA2a pump activity, ularitide and carperitide which are ANP(atrial natriuretic peptide) analogues and recombinant relaxin. Some of the targets forCHF include stabilization of ryanodine receptors, renin inhibition, neprilysin inhibition, neuregulins and SERCA2a gene therapy.


CONCLUSIONS
Clinical trials in heart failure must be designed to minimize the risk of "drug failures." Nevertheless, it is hoped that in the days to come, drugs with superior efficacy and safety will eventually be produced from the surge of molecules that are in the pipeline.
Cardiac Clinical Trials & Research, Department of Cardiology, SRM MCH &RC, Kattankulathur, Chennai, Tamil Nadu, India, 603203, melvingeorge2003@gmail.com.
Melvin
M
George
Muthukumar
M
Rajaram
Elangovan
E
Shanmugam
Thangavel Mahalingam
TM
VijayaKumar
D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D015195:Drug Design; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D002317:Cardiovascular Agents