Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor

Future Med Chem. 2009 Sep;1(6):1153-71. doi: 10.4155/fmc.09.89.


Background: The IGF-1 receptor (IGF-1R) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies. Therefore, this receptor has become a major focus for the development of anticancer agents.

Results: Our lead optimization efforts that blended structure-based design and empirical medicinal chemistry led to the discovery of OSI-906, a novel small-molecule dual IGF-1R/insulin receptor (IR) kinase inhibitor. OSI-906 potently and selectively inhibits autophosphorylation of both human IGF-1R and IR, displays in vitro antiproliferative effects in a variety of tumor cell lines and shows robust in vivo anti-tumor efficacy in an IGF-1R-driven xenograft model when administered orally once daily.

Conclusion: OSI-906 is a novel, potent, selective and orally bioavailable dual IGF-1R/IR kinase inhibitor with favorable preclinical drug-like properties, which has demonstrated in vivo efficacy in tumor models and is currently in clinical testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Cell Line
  • Female
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / metabolism
  • Imidazoles / therapeutic use*
  • Mice
  • Mice, Nude
  • Microsomes / metabolism
  • Models, Molecular
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Protein Conformation
  • Pyrazines / chemical synthesis
  • Pyrazines / chemistry
  • Pyrazines / metabolism
  • Pyrazines / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / chemistry
  • Receptor, Insulin / antagonists & inhibitors*
  • Receptor, Insulin / chemistry
  • Xenograft Model Antitumor Assays


  • 3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol
  • Antineoplastic Agents
  • Imidazoles
  • Pyrazines
  • Receptor, IGF Type 1
  • Receptor, Insulin