诱导多能干细胞
SOX2
化学
同源盒蛋白纳米
胚胎干细胞
体细胞
细胞生物学
诱导剂
林28
细胞分化
生物化学
生物
基因
作者
Xinlai Cheng,Hiroki Yoshida,Dena Raoofi,Sawsan Saleh,Hamed Alborzinia,Frank Wenke,Axel R. Göhring,Stefanie Reuter,Nancy Mah,Heiko Fuchs,Miguel A. Andrade‐Navarro,James Adjaye,Sheraz Gul,Jochen Utikal,Ralf Mrowka,Stefan Wölfl
标识
DOI:10.1021/acs.jmedchem.5b00226
摘要
The octamer-binding transcription factor 4 (Oct3/4) is a master gene in the transcriptional regulatory network of pluripotent cells. Repression of Oct3/4 in embryonic stem cells (ESCs) is associated with cell differentiation and loss of pluripotency, whereas forced overexpression in cooperation with other transcriptional factors, such as Nanog, Sox2, and Lin28, can reprogram somatic cells back into pluripotent cells, termed induced pluripotent stem cells (iPSCs). However, random integration and potential tumorigenic transformation caused by viral transduction limit the clinical application of iPSCs. By performing a cell-based high throughput screening (HTS) campaign, we identified several potential small molecules as inducers of Oct3/4 expression. Here we report a lead structure ethyl 2-((4-chlorophenyl)amino)-thiazole-4-carboxylate, termed O4I2, showing high activity in enforcing Oct3/4 expression. On the basis of chemical expansion, we further identified derivatives having increased activities toward Oct3/4 induction. Thus, O4I2 and its derivatives should provide a new class of small molecules suitable for iPSC generation.
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