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Ethyl 2-((4-chlorophenyl)amino)thiazole-4-carboxylate and derivatives are potent inducers of Oct3/4

Item Type:Article
Title:Ethyl 2-((4-chlorophenyl)amino)thiazole-4-carboxylate and derivatives are potent inducers of Oct3/4
Creators Name:Cheng, X. and Yoshida, H. and Raoofi, D. and Saleh, S. and Alborzinia, H. and Wenke, F. and Goehring, A. and Reuter, S. and Mah, N. and Fuchs, H.R. and Andrade-Navarro, M.A. and Adjaye, J. and Gul, S. and Utikal, J. and Mrowka, R. and Woelfl, S.
Abstract: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. Performing a cell-based High Throughput Screening (HTS) we identified several potential small molecules as inducers of Oct3/4 expression. Here we report a lead structure ethyl 2-(4-chlorophenylamino)-thiazole-4-carboxylate, termed O4I2, showing high activity in enforcing Oct3/4 expression. Based on chemical expansion we further identified derivatives having increased activity towards Oct3/4 induction. Thus O4I2 and its derivatives should provide a new class of small molecules suitable for iPSC generation.
Keywords:iPSCs, Oct3/4 Activator, Stem Cell, Pluripotent, High Throughput Screening, Small Molecule, Chemical Reprogramming, 2-Aminothiazole
Source:Journal of Medicinal Chemistry
ISSN:0022-2623
Publisher:American Chemical Society (U.S.A.)
Volume:58
Number:1
Page Range:5742-5750
Date:13 August 2015
Official Publication:https://doi.org/10.1021/acs.jmedchem.5b00226
PubMed:View item in PubMed

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