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NVP-AEW541

CAS No. : 475489-16-8

MCE 国际站：NVP-AEW541

产品活性：NVP-AEW541 (AEW541) 是一种有效的 IGF-1R 抑制剂，IC₅₀ 为 0.15 μM，也抑制 InsR，IC₅₀ 为 0.14 μM。

研究领域：Protein Tyrosine Kinase/RTK  |  Autophagy

作用靶点：IGF-1R  |  Insulin Receptor  |  Autophagy

In Vitro: NVP-AEW541 inhibits the in vitro kinase activity of the recombinant IGF-IR kinase domain with an IC50 value of 0.15 μM and to be equipotent against the recombinant InsR kinase domain. NVP-AEW541 is confirmed active toward the IGF-IR kinase (IC₅₀=86 nM) and shown to be selective at the cellular level. Indeed, NVP-AEW541 is found to be 27-fold more potent toward the native IGF-IR, as compared to the structurally related native InsR (IC₅₀=2.3 μM). NVP-AEW541 suppresses the IGF-I-mediated survival, soft agar and proliferation of MCF-7 cells with IC₅₀ of 0.162 μM, 0.105 μM and 1.64 μM, respectively.

In Vivo: Oral administration of NVP-AEW541 (20, 30, or 50 mg/kg) results in abrogation of basal and IGF-I-induced receptor, and PKB and MAPK phosphorylation in the NWT-21 tumor xenograft. NVP-AEW541 is administered by oral gavage [50 mg/kg in 0.2 mL of 25 mM L-(+)-tartaric acid] twice a day for 14 consecutive days. The control group is similarly treated with 0.2 mL carrier [25 mM L-(+)-tartaric acid] twice a day. Tumor volume and animal weight are measured thrice a week till the end of the treatment. At that time, animals are sacrificed and tumors are collected and formalin fixed for histologic and immunohistochemical analyses. In both cases, NVP-AEW541 treatment causes tumor shrinkage that reached the statistical significance (P=0.0156 and P=0.0111 for HTLA-230 and SK-N-BE2c, respectively).

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