IDE1

IDE1 is a small-molecule compound that promotes the differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) into definitive endoderm (DE) lineages. It functions by activating the TGF-β signaling pathway, leading to Smad2 phosphorylation and increased Nodal expression. IDE1 has an EC₅₀ of approximately 125 nM for inducing DE differentiation.

Key features and applications include:

• Definitive Endoderm Induction: Efficiently induces Sox17⁺/FoxA2⁺ endodermal progenitors from both mouse and human ESCs.
• TGF-β Pathway Activation: Mimics Activin A by triggering Smad2 phosphorylation, a key step in endoderm specification.
• Cell-Permeable & Cost-Effective: Offers a small-molecule alternative to expensive growth factors like Activin A.
• Versatile in Culture Systems: Effective in both 2D monolayer and 3D embryoid body (EB) differentiation protocols.
• Pancreatic Lineage Differentiation: When combined with FGF10, retinoic acid, or hedgehog inhibitors, IDE1-derived DE cells can further differentiate into Pdx1⁺ pancreatic progenitors.

Research Applications:

• Stem cell differentiation protocols
• Developmental biology studies
• Pancreatic and hepatic lineage specification
• High-throughput screening for endoderm inducers

Relevant disease states include:

• Diabetes Mellitus: IDE1 is used in protocols to generate pancreatic β-cell precursors, aiding in diabetes research and regenerative therapy development.
• Liver Disease: Supports the generation of hepatocyte-like cells from pluripotent stem cells for liver disease modeling and drug screening.
• Congenital Gut Disorders: Enables modeling of early gut tube development and related congenital abnormalities.
• Stem Cell Therapy Research: Facilitates the development of cell-based therapies by providing a scalable method for generating endodermal derivatives.