Structure-Activity Relationship Analysis of YM155 for Inducing Selective Cell Death of Human Pluripotent Stem Cells
- 주제(키워드) stemotoxics , naphthoquinone imidazolium , SAR (structure-activity relationship) , human pluripotent stem cells , teratoma , YM155
- 주제(기타) Chemistry, Multidisciplinary
- 설명문(일반) [Go, Young-Hyun; Jeong, Ho-Chang] Sogang Univ, Coll Nat Sci, Dept Life Sci, Seoul, South Korea; [Lim, Changjin; Chung, Sungkyun; Suh, Young-Ger; Son, Woo Sung; Kim, Seok-Ho] CHA Univ, Coll Pharm, Dept Pharm, Pochen Si, South Korea; [Lim, Changjin; Chung, Sungkyun; Suh, Young-Ger; Son, Woo Sung; Kim, Seok-Ho] CHA Univ, Inst Pharmaceut Sci, Pochen Si, South Korea; [Kwon, Ok-Seon; Lee, Mi-Ok] Korea Res Inst Biosci & Biotechnol, Stem Cell Convergence Res Ctr, Daejeon, South Korea; [Lee, Haeseung; Kim, Wankyu] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea; [Cha, Hyuk-Jin] Seoul Natl Univ, Coll Pharm, Seoul, South Korea; [Cha, Hyuk-Jin] Seoul Natl Univ, Res Inst Pharmaceut Sci, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 FRONTIERS MEDIA SA
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160133
- 본문언어 영어
- Published As http://dx.doi.org/10.3389/fchem.2019.00298
- PubMed https://pubmed.ncbi.nlm.nih.gov/31157201
초록/요약
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.
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