Abstract：
:The discovery of novel small molecules that induce stem cell reprogramming and give efficient access to pluripotent stem cells is of major importance for potential therapeutic applications and may reveal novel insights into the factors controlling pluripotency. Chemical reprogramming of mouse epiblast stem cells (EpiSCs) into cells corresponding to embryonic stem cells (cESCs) is an inefficient process. In order to identify small molecules that promote this cellular transition, we analyzed the LOPAC library in a phenotypic screen monitoring Oct4-GFP expression and identified triamterene (TR) as initial hit. Synthesis of a TR-derived compound collection and investigation for reprogramming of EpiSCs into cESCs identified casein kinases 1 (CK1) α/δ/ɛ as responsible cellular targets of TR and unraveled the structural parameters that determine reprogramming. Delineation of a structure-activity relationship led to the development of Epiblastin A, which engages CK1 isoenzymes in cell lysate and induces efficient conversion of EpiSCs into cESCs.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
Ursu A,Illich DJ,Takemoto Y,Porfetye AT,Zhang M,Brockmeyer A,Janning P,Watanabe N,Osada H,Vetter IR,Ziegler S,Schöler HR,Waldmann Hdoi
10.1016/j.chembiol.2016.02.015subject
Has Abstractpub_date
2016-04-21 00:00:00pages
494-507issue
4eissn
2451-9456issn
2451-9448pii
S2451-9456(16)30085-Xjournal_volume
23pub_type
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