OSI-906 (Linsitinib) is an orally-available, ATP-competitive, imidazopyrazine-based dual inhibitor of IGF-R1 and IR with IC50 biochemical potency of 35 nM and 75 nM, respectively. [1] In vitro cell assays reveal that OSI-906 potently inhibits IGF-1R, pERK1/2, and p-70S6K at IC50s of 24, 28, and 60 nM, respectively. In HT-29 and Colo205 CRC cells, oSI-906 fully inhibits both IR and IGF-1R phosphorylation, with antiproliferative effects at EC50 of 210 nM and 320 nM, respectively.

Oral, in vivo efficacy studies (QDx12) of OSI-906 in a LISN xenograft model resulted in a dose-dependent effect on tumor growth inhibition with 100% TGI and 55% regression at 75 mg/kg, and 60% TGI at 25 mg/kg.