COMMENT This compound is a potent inhibitor of IGF-1R with cellular activity. Even though the compound has been screened against only a small number of other kinases, it shows some off-target activity, at least in biochemical assays. This compound is orally bioavailable and has been employed in in vivo experiments. It's selectivity profile has not been broadly defined. Jun 12 2016 - 2:30pm; 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. Jun 30 2016 - 4:06am; NVP-AEW541 is a potent inhibitor of IGF-1R and is useful for biochemical, cellular and in vivo studies. I recommend it for use with the caveat that its characterization is incomplete. It was reported prior to the availability of methods for the broad evaluation of kinase activity, and there is some degree of off-target activity even in the narrower characterization it has received. Sep 12 2016 - 6:46pm

DESCRIPTION NVP-AEW541 is a potent and selective inhibitor of the receptor tyrosine kinase, insulin-like growth factor I receptor (IGF1R) . It was tested in preclinical studies. (GtoPdb)

MOA Inhibitor (Chemical Probes.org)

DESCRIPTION AEW541, also known as NVP-AEW541, is a novel, potent IGF-IR kinase inhibitor. NVP-AEW541 is capable of distinguishing between the IGF-IR (IC50 = 0.086 microM) and the closely related InsR (IC50 = 2.3 microM) in cells. NVP-AEW541 abrogates IGF-I-mediated survival and colony formation in soft agar at concentrations that are consistent with inhibition of IGF-IR autophosphorylation. NVP-AEW541 represents a class of selective, small molecule IGF-IR kinase inhibitors with proven in vivo antitumor activity and potential therapeutic application. (BOC Sciences Bioactive Compounds)

DESCRIPTION NVP-AEW541 is a selective inhibitor of Insulin-like growth factor 1 receptor (IGF-1R) kinase. It abrogates IGF-I-mediated survival and colony formation in soft agar at concentrations that are consistent with inhibition of IGF-IR autophosphorylation. In vivo, NVP-AEW541 inhibits IGF-IR signaling in tumor xenografts and significantly reduces the growth of IGF-IR-driven fibrosarcomas. (BOC Sciences Bioactive Compounds)