title: Peptidomimetic small-molecule compounds promoting cardiogenesis of stem cells.
abstract: Embryonic stem (ES) cells may be used as an alternative source of functionally intact cardiomyocytes for ischemic heart disease. Several natural and synthetic small molecules have been identified as useful tools for controlling and manipulating stem cell renewal and differentiation. Currently, there is an urgent requirement for novel small molecules that specifically induce differentiation of stem cells into cardiomyocytes. To identify compounds that promote cardiomyogenesis of stem cells, cell-based screening of a peptidomimetic small-molecule library was carried out. A series of β-turn peptidomimetic compounds, including CW209E, increased the expression of α-MHC promoter-driven enhanced green fluorescent protein (EGFP) and ratio of beating embryoid bodies (EBs) without inducing cytotoxicity in mouse embryonic stem cells. CW209E also increased the number of beating EBs in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Thus, this chemical compound should be useful for elucidation of the molecular pathway of cardiogenesis and generation of cardiomyocytes ex vivo, which can be further applied for experimental or clinical cell therapy for ischemic heart diseases.
authors.affiliation: Central Research Institute, JW Pharmaceutical Corporation, Hwaseong 445-380, Korea.
authors.forename: Se-Woong
authors.initials: SW
authors.lastname: Oh
authors.forename: Jung Bok
authors.initials: JB
authors.lastname: Lee
authors.forename: Bora
authors.initials: B
authors.lastname: Kim
authors.forename: Sejin
authors.initials: S
authors.lastname: Jeon
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Ki-Hoan
authors.initials: KH
authors.lastname: Nam
authors.forename: Jong-Ryul
authors.initials: JR
authors.lastname: Ha
authors.forename: Mickie
authors.initials: M
authors.lastname: Bhatia
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D058732:Embryoid Bodies / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology / Q000633:toxicity; D057166:High-Throughput Screening Assays; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology / Q000633:toxicity; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D057786:Peptidomimetics / Q000494:pharmacology* / Q000633:toxicity; D011401:Promoter Regions, Genetic; D054852:Small Molecule Libraries
chemical_list: C580983:CW209E; D006576:Heterocyclic Compounds, 4 or More Rings; D006845:Hydrocarbons, Fluorinated; D057786:Peptidomimetics; D054852:Small Molecule Libraries; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018995:Myosin Heavy Chains