NVP-AEW541 (AEW541) is an orally active inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with an IC50 of 0.15 μM. It also inhibits the insulin receptor (InsR) with an IC50 of 0.14 μM, showcasing significant antitumor activity[1].
体内研究
Oral doses of NVP-AEW541 (20, 30, or 50 mg/kg) effectively inhibit basal and IGF-I-induced receptor phosphorylation, as well as PKB and MAPK activation, in NWT-21 tumor xenografts[1].
Further, NVP-AEW541 administered at 50 mg/kg twice daily for 14 days in 0.2 mL of 25 mM L-(+)-tartaric acid demonstrates significant tumor shrinkage in HTLA-230 and SK-N-BE2c xenograft models, achieving statistical significance with P-values of 0.0156 and 0.0111, respectively. Animals are monitored for tumor volume and weight thrice weekly until sacrifice for histological and immunohistochemical analyses[2].
体外研究
In vitro, NVP-AEW541 blocks kinase activity of both recombinant IGF-IR and InsR kinase domains effectively, with notable potency against native IGF-IR—27 times more than against native InsR (IC50=2.3 μM). It significantly suppresses IGF-I-mediated survival, growth in soft agar, and proliferation of MCF-7 cells, with respective IC50 values of 0.162 μM, 0.105 μM, and 1.64 μM[1].
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