Linsitinib | Inhibits IGF-1R kinase and InsR kinase

Linsitinib (867160-71-2) is a potent and selective dual inhibitor of insulin-like growth factor 1 (IGF-1R) kinase and insulin receptor (InsR) kinase (IC₅₀’s = 35 and 75 nM respectively).¹  It has been investigated as a chemotherapeutic in combination with other drugs for various cancers.^2-6

References/Citations:

1) Mulvihill et al. (2009), Discovery of OSI-906: a selective and orally efficacious inhibitor of the IGF-1 receptor and insulin receptor; Future Med. Chem. 1 1153
2) Bendell et al. (2015), A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer; Invest. New Drugs 33 187
3) Pivonello et al. (2016), The dual targeting of insulin and insulin-like growth factor 1 receptor enhances the mTOR inhibitor-mediated antitumor efficacy in hepatocellular carcinoma ; Oncotarget 7 9718
4) Lee et al. (2016), Inhibition of IGF1R signaling abrogates resistance to afatinib (BIBW2992) in EGFR T790M mutant lung cancer cells; Mol. Carcinog. 55 991
5) Macaulay et al. (2016), Phase I Dose-Escalation Study of Linsitinib (OSI-906) and Erlotinib in Patients with Advanced Solid Tumors; Clin. Cancer Res. 22 2897
6) De Lint et al. (2016), Sensitizing Triple-Negative Breast Cancer to PI3K Inhibition by Cotargeting IGF1R; Mol. Cancer Ther. 15 1545