osi-906 and Neoplasms
osi-906 has been researched along with Neoplasms* in 2 studies
Other Studies
2 other study(ies) available for osi-906 and Neoplasms
| Article | Year |
|---|---|
Potent and selective cyclohexyl-derived imidazopyrazine insulin-like growth factor 1 receptor inhibitors with in vivo efficacy.
Preclinical and emerging clinical evidence suggests that inhibiting insulin-like growth factor 1 receptor (IGF-1R) signaling may offer a promising therapeutic strategy for the treatment of several types of cancer. This Letter describes the medicinal chemistry effort towards a series of 8-amino-imidazo[1,5-a]pyrazine derived inhibitors of IGF-1R which features a substituted quinoline moiety at the C1 position and a cyclohexyl linking moiety at the C3 position. Lead optimization efforts which included the optimization of structure-activity relationships and drug metabolism and pharmacokinetic properties led to the identification of compound 9m, a potent, selective and orally bioavailable inhibitor of IGF-1R with in vivo efficacy in an IGF-driven mouse xenograft model. Topics: Animals; Antineoplastic Agents; Benzimidazoles; Imidazoles; Mice; Neoplasms; Protein Kinase Inhibitors; Pyrazines; Receptor, IGF Type 1; Structure-Activity Relationship; Transplantation, Heterologous | 2011 |
Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor.
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.. 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.. 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. Topics: Animals; Antineoplastic Agents; Cell Line; Female; Humans; Imidazoles; Mice; Mice, Nude; Microsomes; Models, Molecular; Molecular Structure; Neoplasms; Protein Conformation; Pyrazines; Rats; Rats, Sprague-Dawley; Receptor, IGF Type 1; Receptor, Insulin; Xenograft Model Antitumor Assays | 2009 |