Linsitinib, Free Base (OSI-906, OSI 906AA, CAS 867160-71-2), >99%

LC Laboratories' Product Number L-5814 - Linsitinib, Free Base (OSI-906, OSI 906AA, CAS 867160-71-2), >99% - for research use only. Linsitinib, also known as OSI-906, is a novel, potent small-molecule dual insulin-like growth factor-1 receptor (IGF-1R)/insulin receptor (IR) kinase inhibitor.Linsitinib inhibited IGF-1R and IR kinases with IC50 values of 35 nM and 75 nM, respectively. Linsitinib potently and selectively blocked autophosphorylation of both human IGF-1R and IR, inhibited the proliferation of a variety of tumor cell lines in vitro, and displayed robust in vivo anti-tumor efficacy in an IGF-1R-driven xenograft model when administered orally. Linsitinib showed superior efficacy compared with MAB391, a selective anti-IGF-1R antibody, in human tumor xenograft models in which both IGF-1R and IR were phosphorylated. Following a single dose of linsitinib, [18]FDG-PET was shown to serve as a rapid, noninvasive pharmacodynamic biomarker of IGF-1R/IR inhibition. IGF-1 was shown to be overexpressed in low-grade serous ovarian carcinoma (SOC) when compared with serous borderline ovarian tumors (SBOTs) and high-grade SOCs. Low-grade SOC cell lines were more sensitive to IGF-1 stimulation and IGF-1R inhibition than were high-grade lines. Therefore, the IGF-1 pathway is a potential therapeutic target in low-grade SOC. Linsitinib blocked IGF-1 signaling in LCC6 xenograft tumors in vivo. When given once a week, combined administration simultaneously of OSI-906 and doxorubicin significantly improved the anti-tumor effect of doxorubicin. Therapeutic targeting of both IR and IGF-1R by linsitinib was shown to be more effective than targeting IGF-1R alone by MAB391 in abrogating resistance to endocrine therapy in breast cancer. Epithelial-mesenchymal transition (EMT) was demonstrated to predict hepatocellular carcinoma cell sensitivity to linsitinib, as the epithelial phenotype was strongly associated with expression of IGF-2 and IR, and activation of IGF-1R and IR. Induction of EMT by TGFβ reduced sensitivity to linsitinib.

• Supplier: LC Laboratories
• Product #: L-5814
• Sku #: L-5814_500mg