NVP-AEW541

439, 55

Female Harlan athymic nude mice weighing 18-25 g with NWT-21 cells

ca. 10 uM

Dissolved in 25 mM L(+)-tartaric acid

NVP-AEW541 also inhibits InsR, Tek, Flt1 and Flt3 with IC50 of 140 nM, 530 nM, 600 nM and 420 nM in purified kinases/recombinant kinase domains assay. NVP-AEW541 is more selective and shows 27-fold more potent than InsR at the cellular level. 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. NVP-AEW541 also reduces the level of phospho-IGF-1R and phospho-PKB in NWT-21 cells., [1] NVP-AEW541 shows growth inhibitory effect on TC-71 musculoskeletal sarcoma cells in low-serum medium as well as in 10% FBS–containing medium. NVP-AEW541 inhibits cell cycle progression and induces specific G1 arrest in sarcoma cell lines (TC-71, SK-N-MC, SaoS-2, RD/18 and RH4). [2] NVP-AEW541 could inhibit the growth of human neuroblastoma cells with IC50 of 0.4-6.8 uM. An increase in the hypodiploid fraction and the depletion of the S and G2-M compartments could be detected in these cell lines. NVP-AEW541-driven inhibition of IG1R causes a reduction of phosphorylation of Akt, but not of Erk1 and Erk2 in neuroblastoma cells. [3] NVP-AEW541 inhibits glioma cell growth and disrupts the autocrine loop initiated by HIF1alpha stabilization. [4] A recent study shows that NVP-AEW541 suppresses the proliferation and viability of PC3, DU145, and 22Rv1 prostate cancer cells, without necessarity of associated cell death. NVP-AEW541 decreases phospho-Akt levels in 22Rv1 and DU415 cells but not PC3 cells, without affecting total Akt levels, which shows that PTEN status could determine the effectiveness of NVP-AEW541 with essential Akt. NVP-AEW541-induced radiosensization is dependent on Akt activation status. NVP-AEW541 could increase the H2AX phosphorylation (a measure of DSBs) in PC3, DU145, and 22Rv1 cells. [5]

72 hours

Between 3, 103 and 6, 103 cells/well are seeded in 96-well plates with a total media volume of 100 uL/well. Increasing concentrations of NVP-AEW541 is added 24 hours thereafter in quadruplicate. 72 hours later, cells are fixed by addition of 25 uL/well Glutaraldehyde (20%) and incubation for 10 min at RT. Cells are then washed 2 with 200 uL/well H2O and 100 uL Methylene Blue (0.05%) is added. After incubation for 10 min at RT, cells are washed 3 with 200 uL/well H2O. 200 uL/well HCl (3%) is added, and following incubation for 30 min at RT on a plate shaker, absorbance is measured at 650 nm.

NVP-AEW541 is a potent inhibitor of IGF-1R/InsR with IC50 of 150 nM/140 nM in cell-free assays, greater potency and selectivity for IGF-1R in a cell-based assay.