IDE 2 is a definitive endoderm inducer with small molecule activity and activates the TGF-β/Nodal signaling pathway. IDE 2 upregulates Sox17 and FoxA2 expression to drive human pluripotent stem cells to ectoderm-external lineage specification. IDE 2 can be used for definitive endoderm differentiation and human embryonic stem cell fate regulation studies[1-4].
In vitro, 200nM IDE 2 was applied to umbilical cord blood-derived stem cells for 4 days and induced the stem cells to change into a round morphology and upregulate Brachyury mRNA[5]. 1μM IDE 2 was applied to embryonic stem cells for 4 days and induced the cells to express definitive endoderm markers FOXA2 and SOX17[6].
References:[1] Korostylev A, Mahaddalkar PU, Keminer O,et al. A high-content small molecule screen identifies novel inducers of definitive endoderm. Mol Metab. 2017 May 4;6(7):640-650.
[2] Novakovsky G, Sasaki S, Fornes O,et al. In silico discovery of small molecules for efficient stem cell differentiation into definitive endoderm. Stem Cell Reports. 2023 Mar 14;18(3):765-781.
[3] Bogacheva MS, Harjumäki R, Flander E, et al. Differentiation of Human Pluripotent Stem Cells Into Definitive Endoderm Cells in Various Flexible Three-Dimensional Cell Culture Systems: Possibilities and Limitations. Front Cell Dev Biol. 2021 Sep 9;9:726499.
[4] Xu T, Zhang M, Laurent T, et al. Concise review: chemical approaches for modulating lineage-specific stem cells and progenitors. Stem Cells Transl Med. 2013 May;2(5):355-61.
[5] Borowiak M, Maehr R, Chen S, et al. Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells. Cell Stem Cell. 2009 Apr 3;4(4):348-58.
[6] Filby CE, Williamson R, van Kooy P, et al. Stimulation of Activin A/Nodal signaling is insufficient to induce definitive endoderm formation of cord blood-derived unrestricted somatic stem cells. Stem Cell Res Ther. 2011 Apr 4;2(2):16.