NVP-AEW541

475489-16-8

C27H29N5O

DMSO : >= 51 mg/mL (116.03 mM)

Protein Tyrosine Kinase/RTK; Protein Tyrosine Kinase/RTK; Autophagy

NVP-AEW541 is a potent inhibitor of IGF-1R with IC₅₀ of 0.15 uM, also inhibits InsR, with IC₅₀ of 0.14 uM. IC50 & Target: IC50: 0.15 +/-0.036 uM (IGF-IR), 0.14+/-0.039 uM (InsR), 0.42+/-0.11 uM (Flt-3), 2+/-0.61 uM (PDGFR), 2.4+/-0.38 uM (c-Src), 3.3+/-1.4 uM (c-Kit)^[1] In Vitro: NVP-AEW541 inhibits the in vitro kinase activity of the recombinant IGF-IR kinase domain with an IC50 value of 0.15 uM 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 uM). NVP-AEW541 suppresses the IGF-I-mediated survival, soft agar and proliferation of MCF-7 cells with IC₅₀ of 0.162 uM, 0.105 uM and 1.64 uM, respectively^[1]. 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^[1]. 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)^[2].