This probe is suggested to be selective ATP-competitive inhibitor of IGF-1R, and to the lesser extent IR. The original paper (Cancer Cell. 2004 Mar;5(3):231-9) reports a 150 nM IC50 for IGF-1R and 140 nM IC50 for IR in vitro. In cell based assays that monitor autophosphorylation of IGF-1R and IR, the compound is more selective for IGF-1R (IC50 86 nM for IGF-1R and 2300 nM for IR). Based on in vitro biochemical assays compound potently inhibit kinase TEK, FLT-1, and FLT-3. Since kinome-wide selectivity of the probe was not evaluated, it can potentially inhibit other kinases in cells. The second paper (Cancer Res. 2005 May 1;65(9):3868-76); however, shows the correlation between the sensitivity of Ewing's Sarcoma, osteosarcoma and rhabdomyosarcoma cells to NVP-AEW541. This suggests that the compound had a major effect in those cell lines due to the inhibition of IGF-1R. Users should always confirm that NVP-AEW541 does not inhibit AKT phosphorylation upon EGF stimulation and does not inhibit IR autophosphorylation, to confirm selectivity. The original paper reports the inhibition of IGF-1R phosphorylation in vivo; however, data to confirm selectivity at the doses used were not provided.
6 May 2016 )