Heart regeneration: opportunities and challenges for drug discovery with novel chemical and therapeutic methods or agents.
Following a heart attack, more than a billion cardiac muscle cells (cardiomyocytes) can be killed, leading to heart failure and sudden death. Much research in this area is now focused on the regeneration of heart tissue through differentiation of stem cells, proliferation of existing cardiomyocytes and cardiac progenitor cells, and reprogramming of fibroblasts into cardiomyocytes. Different chemical modalities (i.e. methods or agents), ranging from small molecules and RNA approaches (including both microRNA and anti-microRNA) to modified peptides and proteins, are showing potential to meet this medical need. In this Review, we outline the recent advances in these areas and describe both the modality and progress, including novel screening strategies to identify hits, and the upcoming challenges and opportunities to develop these hits into pharmaceuticals, at which chemistry plays a key role.
Department of Medicinal Chemistry, Cardiovascular and Metabolic Diseases Innovative Medicines, AstraZeneca, Pepparedsleden 1, Mölndal, 43183 (Sweden). alleyn.plowright@astrazeneca.com.
Alleyn T
AT
Plowright
Ola
O
Engkvist
Adrian
A
Gill
Laurent
L
Knerr
Qing-Dong
QD
Wang
D002454:Cell Differentiation; D055808:Drug Discovery; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D044968:Regenerative Medicine / Q000379:methods*
cardiomyocytes; chemical modalities; drug discovery; heart regeneration