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Structure-Activity Relationship Analysis of YM155 for Inducing Selective Cell Death of Human Pluripotent Stem Cells

Title
Structure-Activity Relationship Analysis of YM155 for Inducing Selective Cell Death of Human Pluripotent Stem Cells
Authors
Go, Young-HyunLim, ChangjinJeong, Ho-ChangKwon, Ok-SeonChung, SungkyunLee, HaeseungKim, WankyuSuh, Young-GerSon, Woo SungLee, Mi-OkCha, Hyuk-JinKim, Seok-Ho
Ewha Authors
김완규
SCOPUS Author ID
김완규scopus
Issue Date
2019
Journal Title
FRONTIERS IN CHEMISTRY
ISSN
2296-2646JCR Link
Citation
FRONTIERS IN CHEMISTRY vol. 7
Keywords
stemotoxicsnaphthoquinone imidazoliumSAR (structure-activity relationship)human pluripotent stem cellsteratomaYM155
Publisher
FRONTIERS MEDIA SA
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
Despite great potential for regenerative medicine, the high tumorigenic potential of human pluripotent stem cells (hPSCs) to form undesirable teratoma is an important technical hurdle preventing safe cell therapy. Various small molecules that induce the complete elimination of undifferentiated hPSCs, referred to as "stemotoxics," have been developed to facilitate tumor-free cell therapy, including the Survivin inhibitor YM155. In the present work, based on the chemical structure of YM155, total 26 analogs were synthesized and tested for stemotoxic activity toward human embryonic stem cells (hESCs) and induced PSCs (iPSCs). We found that a hydrogen bond acceptor in the pyrazine ring of YM155 derivatives is critical for stemotoxic activity, which is completely lost in hESCs lacking SLC35F2, which encodes a solute carrier protein. These results suggest that hydrogen bonding interactions between the nitrogens of the pyrazine ring and the SLC35F2 protein are critical for entry of YM155 into hPSCs, and hence stemotoxic activity.
DOI
10.3389/fchem.2019.00298
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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