Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor.
Article Details
- CitationCopy to clipboard
Mulvihill MJ, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, O'Connor M, Pirritt C, Sun Y, Yao Y, Arnold LD, Gibson NW, Ji QS
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.
- PubMed ID
- 21425998 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Linsitinib Insulin receptor Protein Humans UnknownInhibitorDetails