A small molecule that directs differentiation of human ESCs into the pancreatic lineage

Nat Chem Biol. 2009 Apr;5(4):258-65. doi: 10.1038/nchembio.154. Epub 2009 Mar 15.


Stepwise differentiation from embryonic stem cells (ESCs) to functional insulin-secreting beta cells will identify key steps in beta-cell development and may yet prove useful for transplantation therapy for diabetics. An essential step in this schema is the generation of pancreatic progenitors--cells that express Pdx1 and produce all the cell types of the pancreas. High-content chemical screening identified a small molecule, (-)-indolactam V, that induces differentiation of a substantial number of Pdx1-expressing cells from human ESCs. The Pdx1-expressing cells express other pancreatic markers and contribute to endocrine, exocrine and duct cells, in vitro and in vivo. Further analyses showed that (-)-indolactam V works specifically at one stage of pancreatic development, inducing pancreatic progenitors from definitive endoderm. This study describes a chemical screening platform to investigate human ESC differentiation and demonstrates the generation of a cell population that is a key milepost on the path to making beta cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Carcinogens / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Line
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects*
  • Embryonic Stem Cells / physiology
  • Homeodomain Proteins / metabolism
  • Humans
  • Indoles / pharmacology*
  • Insulin-Secreting Cells / cytology*
  • Lactams / pharmacology*
  • Mice
  • Trans-Activators / metabolism


  • Biomarkers
  • Carcinogens
  • Homeodomain Proteins
  • Indoles
  • Lactams
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • indolactam V

Associated data

  • PubChem-Substance/57244616
  • PubChem-Substance/57244617
  • PubChem-Substance/57244618
  • PubChem-Substance/57244619
  • PubChem-Substance/57244620
  • PubChem-Substance/57244621
  • PubChem-Substance/57244622
  • PubChem-Substance/57244623
  • PubChem-Substance/57244624
  • PubChem-Substance/57244625
  • PubChem-Substance/57244626
  • PubChem-Substance/57244627
  • PubChem-Substance/57244628
  • PubChem-Substance/57244629
  • PubChem-Substance/57244630
  • PubChem-Substance/57244631
  • PubChem-Substance/57244632
  • PubChem-Substance/57244633
  • PubChem-Substance/57244634