Recent advances in the development of cyclin-dependent kinase inhibitors as new therapeutics in oncology and cardiology

Small molecules and human cardiomyogenesis: Is there a bottleneck in current research?

“…The major phases in cardiac development are as follows: (1) establishment of mesoderm formation (from hPSCs); (2) patterning toward cardiac mesoderm; (3) cardiac mesoderm formation; (4) cardiomyocyte development and maturation [10][11][12]. Temporal regulation of metabolic and signaling pathways is key crucial for successful hPSCs differentiation to CMs, as demonstrated by previously published experimental data [2,6,7,10,11]. Each stage of this gradual transition between cell types can be monitored via the detection of temporally specific biomarkers like transcription factors (e.g.…”

“…For over a decade now the number of reports regarding small-molecule compounds with cardiomyogenic potential and molecular pathways of hPSC differentiation into cardiomyocytes has increased exponentially [4][5][6]. As a result, novel small moleculedirected differentiation protocols for derivation of hPSCderived CMs have been developed [2,6]. In this regard Karakikes and co-workers [7] have reported a methodology for CM differentiation, based on modulation of the canonical Wnt pathway via the small molecule IWR-1, with an efficiency close to 100%.…”

“…However, it must be stated that the canonical Wnt pathway is one of the most extensively studied and commonly used pathways for inducing cardiomyogenesis in hPSCs via small molecules [2,6,[10][11][12]. This implies a rather intriguing question: "Is the potential of hPSC-derived CMs in areas such as drug discovery, disease modeling and regenerative therapies still limited due to our current understanding of human biology?…”

“…This research enthusiasm, notwithstanding, a "revolution" in stem cell biology has being stirring up for some time. For over a decade now the number of reports regarding small-molecule compounds with cardiomyogenic potential and molecular pathways of hPSC differentiation into cardiomyocytes has increased exponentially [4][5][6]. As a result, novel small moleculedirected differentiation protocols for derivation of hPSCderived CMs have been developed [2,6].…”

Human pluripotent stem-cell-derived cardiomyocytes in cardiovascular drug discovery and development

“…This has provided grounding for cardiovascular drug discovery and development testing to be carried out [19]. The mini-hearts contract regularly, and similarly, to normal human cardiac muscle and can be treated with various drug compounds.…”