NVP-AEW541

Catalog No.S1034 Synonyms: AEW541

NVP-AEW541 Chemical Structure

Molecular Weight(MW): 439.55

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.

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Cited by 23 Publications

7 Customer Reviews

  • (A) KRAS mutant (SW837 and LoVo) or KRAS/PIK3CA mutant (HCT-116) colorectal cancers were treated with the indicated compounds for 6 hours (gef, gefitinib 1 μM; NVP, NVP-AEW541 1 μM; PHA, PHA-665752 1 μM), and the resulting protein lysates were immunoprecipitated with an anti-p85 antibody. The precipitated proteins were analyzed by Western blots with the indicated antibodies. Whole cell extracts were probed with the indicated antibodies. Asterisks indicate the IRS proteins for SW837 and HCT-116 cells, and ERBB3 for LoVo cells. (B) SW837 cells were grown in either normal serum (5% FBS) or low serum (0.5% FBS) and treated with vehicle, R1507 anti–IGF-IR antibody (25 μg/ml), or NVP-AEW541 (1 μM) for 6 hours. The cells were lysed and probed with the indicated antibodies.

    J Clin Invest 2011 121, 4311-21. NVP-AEW541 purchased from Selleck.

    A, cell viability reduction. TC1889 cells were treated with pharmacological inhibitors against IGF-1R (NVP and BMS), as well as a neutralizing IGF-1R antibody (aIR3) and cell viability was assessed using MTT-assays. Mouse IgG1 antibody was employed as a reference control for the effects of aIR3 at respective concentrations. Assays were performed in sextuple. Data are expressed as the mean SD (n 3). B, induction of cell death. TC1889 cells were treated with pharmacological inhibitors against IGF-1R as well as a neutralizing IGF-1R antibody and cell death was evaluated by FACS-analyses following PI-staining. Data are expressed as the mean SD (n ?3).

    Clin Cancer Res 2011 17, 2237-2249. NVP-AEW541 purchased from Selleck.

  • C, TC1889 cells were serum-starved for 16 hours, treated with vehicle or the IGF-1R inhibitor PPP, NVP, BMS, or the neutralizing IGF1R antibody aIR3 for 2 hours, and then stimulated with IGF-I (100 ng/mL) for 15 min. The activity of PI3K/Akt- and MAPK/Erk-signaling was investigated by an analysis of the expression of phosphorylated Akt, GSK3b, MEK1/2, and Erk using Western immunoblotting. Representative results are shown (n ?3). Actin served as a loading control. D, TC1889 cells were treated with vehicle or PPP, NVP, BMS, or aIR3. The activity of PI3K/Akt- and MAPK/Erk-signaling was investigated as mentioned earlier. Representative results are shown (n ?3). Actin served as a loading control.

    Clin Cancer Res 2011 17, 2237-2249. NVP-AEW541 purchased from Selleck.

    Inhibition of IGF-IR/InsR or PI3K abrogates AKT membrane localization and phosphorylation. MCF-7/LTED cells were transfected with an AKT PH-GFP plasmid. On day four, cells were treated with 100 ng/ml IGF-I in serum-free medium for 15 minutes, or pre-incubated with 10% DCC-FBS ?1 uM AEW541 or 1 uM BKM120 for 30 minutes followed by treatment with 2 uM AZD5363 for four hours. Cells were viewed in a LSM 510Meta confocal microscope at 40x magnification.

    Breast Cancer Res 2013 15, R55. NVP-AEW541 purchased from Selleck.

  • A, cell viability assay for mouse rhabdomyosarcoma cultures treated with various doses of NVP-AEW541 and immunoblot showing expression levels of Igf1r in mouse rhabdomyosarcoma primary cell cultures (U20325 and U21089) compared with the mouse myoblast cell line C2C12. B, anchorage-dependent colony formation assay showing increased inhibition of colony formation by mouse rhabdomyosarcoma cultures compared to mouse myoblast cell line C2C12 on treatment with increasing doses of NVPAEW541. C, anchorageindependent colony formation by mouse rhabdomyosarcoma cultures (U20325) is inhibited on treatment with NVP-AEW541, indicated by a decrease in colony size. The scale bar represents 50mm. The number of colonies formed in soft agar also is reduced on treatment with NVP-AEW541. D, Western blot showing decrease in the phosphorylation of Igf1r, P70 S6 kinase, IRS1, Akt, Mapk, and Shc on treatment of the mouse rhabdomyosarcoma primary cell cultures (U20325) with increasing amounts of NVPAEW541.

    Mol Cancer Ther 2011 10:697-707. NVP-AEW541 purchased from Selleck.

    A, treating the mouse rhabdomyosarcoma primary cell cultures (U20325) with increasing amount of NVP-AEW541 induces cell cycle arrest in the G1 phase. B, at moderately high concentrations of NVP-AEW541, the mouse rhabdomyosarcoma cells (U20325) show increased apoptosis as evident by the presence of cleaved caspase-3 at 5 mmol/L (but not at 2 mmol/L, unpublished data). C, representative (median) images of luminescence emitted by rhabdomyosarcoma primary cell cultures grown on quail CAM and being treated with DMSO, imatinib, and NVP-AEW541. The images are displayed with a minimum–maximum scale of 2 106 to 2 107 photons/s/cm2/steradian. D, graphical representation of the intensity of bioluminescence signal emitted by rhabdomyosarcoma primary cell cultures grown on quail CAM that were being treated with DMSO, imatinib (100 mmol/L), or NVPAEW541(10 mmol/L).

    Mol Cancer Ther 2011 10:697-707. NVP-AEW541 purchased from Selleck.

  • Combination of NVP-AEW541 and lapatinib cooperatively inhibits the growth of NVP-AEW541 resistant murine rhabdomyosarcoma primary cell cultures with Igf1r/Her2 complexes. Cell viability assay for Naïve, untreated (U20325; A) and NVP-AEW541 innately resistant mouse rhabdomyosarcoma primary culture (U44676; B) treated with varying concentrations of NVP-AEW541, lapatinib, or a combination of both. Naïve cells (U20325) were sensitive to NVP-AEW541, but lapatinib had no cooperativity. In contrast, NVP-AEW541 at moderate doses increased cell growth in resistant cell cultures (U44676). However, this paradoxical effect was reduced by the addition of lapatinib, although lapatinib treatment alone had very little effect. C, the NVP-AEW541 resistant primary tumor cell line (U44676) was treated with DMSO, 5mmol/L lapatinib, 5 mmol/L NVP-AEW541, and a combination of 5 mmol/L NVP-AEW541 t lapatinib for 25 minutes and Western blot analysis was done on lysates for p-Igf1r and p-Her2.

    Mol Cancer Ther 2011 10, 697-707. NVP-AEW541 purchased from Selleck.

Purity & Quality Control

Choose Selective IGF-1R Inhibitors

Biological Activity

Description 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.
Targets
Insulin Receptor [1]
(Cell-free assay)
IGF-1R [1]
(Cell-free assay)
FLT3 [1]
(Cell-free assay)
Tek [1]
(Cell-free assay)
FLT1 [1]
(Cell-free assay)
0.14 μM 0.15 μM 0.42 μM 0.53 μM 0.6 μM
In vitro

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 μM, 0.105 μM and 1.64 μM, 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 μM. 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 IGF-1R 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 HIF1α 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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NWT-21 MYjLbY5ie2ViYYPzZZk> M{fNVZ4yOOLCit88US=> NXjKPVBITE2VTx?= MWjpcohq[mm2czDJS2YuUVJid3n0bEBKSzVyIH;mJFAvODh4INMxJFAvODJ6IN88US=> MlPJNVUxPTB7MUW=
A14 MkPDT4lv[XOnIHHzd4F6 M4HifZ4yOOLCit88US=> MoLlSG1UVw>? M4nJdYlvcGmkaYTzJGlve1Jid3n0bEBKSzVyIH;mJFIvOyEEsTCwMlE3OyEQvF2= MkHRNVUxPTB7MUW=
A431  MofzT4lv[XOnIHHzd4F6 NXfFUVVUhjFy4pEK{txO MmHOSG1UVw>? NEj0eFlqdmirYnn0d{BJTVJzIIfpeIghUUN3MDDv[kA,OTBizszN MX2xOVA2ODlzNR?=
A31  M{C0T2tqdmG|ZTDhd5NigQ>? MoLHglEx6oDMzszN M2juPWROW09? MXzpcohq[mm2czDQSGdHWiC5aYToJGlEPTBib3[gQlExKM7:TR?= MUixOVA2ODlzNR?=
GIST882 NXrTPGxNU2mwYYPlJIF{e2G7 NWO5SXkzhjFy4pEK{txO M3TleGROW09? NVX3fpBocW6qaXLpeJMh[y2NaYSge4l1cCCLQ{WwJI9nKD53IN88US=> M{m4Z|E2ODVyOUG1
32D-Bcr-Abl NYLrV5lyU2mwYYPlJIF{e2G7 NG\3UJh,OTEkgJtOwG0> MWXEUXNQ MYPpcohq[mm2czDCZ5IuSWKuIICyNVAhf2m2aDDJR|UxKG:oIE6xNEDPxE1? M{PYN|E2ODVyOUG1
MCF-7  MUXDfZRwgGmlaYT5JIF{e2G7 M{\md2ROW09? M4HSemlEPTB;MT62OEDPxE1? NYDNWo9POTVyNUC5NVU>
NWT-21 M1nYfGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MUHEUXNQ MmT2TWM2OD1yLkG2N{DPxE1? NXu4VXk1OTVyNUC5NVU>
TC-71 NF\SZXFIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NYj5ZVhIhjFizszN MXvEUXNQ NX3iO2pqcW6qaXLpeJMhcW6|dXzpck1tcWunIHfyc5d1cCCoYXP0c5IuUeLCk33l[IlifGWmIHfyc5d1cA>? MUGxOVg3PzN6Nh?=
TC-71 NFTobWdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NVPTdYRJhjgkgJtOwG0> NXS2WXVITE2VTx?= NIDpXWlKSzVyPECuOUDPxE1? NWHabVUzOTV6NkezPFY>
Saos-2 MUjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NYrDfYU3hjgkgJtOwG0> NGHlSWdFVVOR NXrV[mZJUUN3MEyzJO69VQ>? NHzGRlYyPTh4N{O4Oi=>
U-2OS NYLjTI12T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= M33i[J446oDMzszN Ml31SG1UVw>? NF\BVYJKSzVyPECuOUDPxE1? M4jxdVE2QDZ5M{i2
SK-ES-1 NFrnZ5RIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NI\nUFV,P+LCit88US=> NUjWe|R6TE2VTx?= NIDqdpRKSzVyPECuOUDPxE1? M3nDSVE2QDZ5M{i2
SK-N-MC NV21WnVvT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MkHFglfjiIsQvF2= Ml[2SG1UVw>? NEDrcHVKSzVyPECuOUDPxE1? MkTYNVU5Pjd|OE[=
RD-ES NYOwZoZWT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NEPQdIh,P+LCit88US=> NYLIeIVsTE2VTx?= NF7x[|NKSzVyPECuOUDPxE1? MY[xOVg3PzN6Nh?=
SJ-Rh 30 M2fVd2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M4Djfp446oDMzszN MonoSG1UVw>? MW\JR|UxRDBwNTFOwG0> NUfWXVJYOTV6NkezPFY>
SJ-Rh 4 NUPrXJVJT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NWG1cFN[hjgkgJtOwG0> M3PJVGROW09? MYTJR|UxRDBwNTFOwG0> NE[5RZkyPTh4N{O4Oi=>
6647 MkXRS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MUj+O-KBks7:TR?= MorKSG1UVw>? NXq1VGFSUUN3MEywMlUh|ryP NXLaSFE2OTV6NkezPFY>
SARG M2rSVmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MVX+O-KBks7:TR?= MYLEUXNQ M2DCcGlEPTB:MzFOwG0> NV3uNXFROTV6NkezPFY>
MOS M3zDbWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NH7t[JR,P+LCit88US=> MY\EUXNQ MYjJR|UxRDRizszN NFT0cIEyPTh4N{O4Oi=>
IOR/OS7 MWLHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NVm0OYNXhjgkgJtOwG0> M{nhVmROW09? Mo\aTWM2ODxzIN88US=> M4HmXFE2QDZ5M{i2
IOR/OS9 NEDn[5hIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NFHjR4R,P+LCit88US=> M{HmPWROW09? NUfXbZBKUUN3MEy2JO69VQ>? NGjFfnYyPTh4N{O4Oi=>
IOR/OS10 NEe2TlNIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NF;hTYV,P+LCit88US=> NGTsNnpFVVOR MnHHTWM2ODx3IN88US=> MXKxOVg3PzN6Nh?=
IOR/OS14 MV7Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NXLOcWdQhjgkgJtOwG0> NIO5O29FVVOR NX3BN3RpUUN3MEy0JO69VQ>? NXSwVodQOTV6NkezPFY>
LAP35 MXTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MmK4glfjiIsQvF2= MnzJSG1UVw>? NVrjT4RyUUN3MEywMlUh|ryP MlPyNVU5Pjd|OE[=
IOR/BRZ MXvHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MlXYglfjiIsQvF2= NYjGU2loTE2VTx?= Mlu2TWM2ODxyLkWg{txO MkPWNVU5Pjd|OE[=
IOR/CAR NEPye3lIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= M3X6U5446oDMzszN Mo\TSG1UVw>? MVTJR|UxRDFizszN NHLzd4cyPTh4N{O4Oi=>
IOR/NGR NUPQSJV3T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= M2XPSZ446oDMzszN NYDmfmx5TE2VTx?= MXjJR|UxRDBwNTFOwG0> MmPJNVU5Pjd|OE[=
IOR/RCH NFS3Z5VIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NHjYS|V,P+LCit88US=> NFrLdHpFVVOR NVTIPXZOUUN3MEywMlUh|ryP NUS0bo1sOTV6NkezPFY>
RMZ-RC2 MVHHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MYP+O-KBks7:TR?= Moi3SG1UVw>? NHLSPJdKSzVyPECuOUDPxE1? NYnVVZlWOTV6NkezPFY>
CCA NIm3eY9Iem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MYH+O-KBks7:TR?= NF7rUVJFVVOR NUS1WnhPUUN3MEyyJO69VQ>? MX[xOVg3PzN6Nh?=
RD/18 M2H1Zmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 Mm\sglfjiIsQvF2= NVTVfHo5TE2VTx?= M3ixRWlEPTB:NDFOwG0> MnT5NVU5Pjd|OE[=
OVCAR-3 NGjZVXBIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= Mn\PglE26oDMzszN NFjWenRFVVOR NGDrVFlqdmirYnn0d{Bk\WyuIIDyc4xq\mW{YYTpc44> NFe5VIIyPjNyMEiyNC=>
OVCAR-4 M4DM[Wdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MWj+NVXjiIsQvF2= NXTVN29nTE2VTx?= M33nS4lvcGmkaYTzJINmdGxicILvcIln\XKjdHnvci=> M{jvRlE3OzByOEKw
OVCAR-3 MkC4RZBweHSxc3nzJIF{e2G7 NXrZXHJKhjF34pEK{txO NVK0Sld1TE2VTx?= Mlu5bY5lfWOnczDhdI9xfG:|aYO= M2L0WFE3OzByOEKw
OVCAR-4 M{ex[2Fxd3C2b4Ppd{Bie3OjeR?= MXT+NVXjiIsQvF2= NXvYfotETE2VTx?= NHW0TYZqdmS3Y3XzJIFxd3C2b4Ppdy=> NYfielhZOTZ|MEC4NlA>
OVCAR-3 NGfsOnRHfW6ldHnvckBie3OjeR?= MVL+NVXjiIsQvF2= MWjEUXNQ M4LtPGRm[3KnYYPld{BxcG:|cHjvdplt[XSrb36gc4YhSUuW NVLuc29OOTZ|MEC4NlA>
Huh-7 NFTQVlhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MlXrglEx6oDMzszN MV\EUXNQ MXTJR|UxRTFwNDFOwG0> MUmxOlU{ODd|NB?=
Hep-G2 MlPKS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M3zQW54yOOLCit88US=> MVrEUXNQ MlrETWM2OD1zLkig{txO MlLiNVY2OzB5M{S=
Hep-3B M2PCfGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MkTxglEx6oDMzszN NUjDdZBwTE2VTx?= NYfyPZFXUUN3ME2xMlkh|ryP NHS5W3AyPjV|MEezOC=>
SK-Hep-1 MXTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MlqzglEx6oDMzszN NUPpS4o4TE2VTx?= NEXjUI1KSzVyPU[uPUDPxE1? NUj4fmVzOTZ3M{C3N|Q>
Huh-7 MU\GeY5kfGmxbjDhd5NigQ>? M3XOUp4yOOLCit88US=> MmrqSG1UVw>? MULJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2 NHHj[XEyPjV|MEezOC=>
Hep-G2 Mlr5SpVv[3Srb36gZZN{[Xl? NYHhcI9ChjFy4pEK{txO MYXEUXNQ NYXsVII1UW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> M3;tTlE3PTNyN{O0
SK-Hep-1 M2HMPWZ2dmO2aX;uJIF{e2G7 MWT+NVDjiIsQvF2= NFK1VlRFVVOR NHHkcpBKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0 NUjkdXkxOTZ3M{C3N|Q>
BON MWPLbY5ie2ViYYPzZZk> M1Hpep43KM7:TR?= NIfqTmFFVVOR M3vpWIlv\HWlZYOg[IVxcG:|cHjvdplt[XSrb36gc4YhUUeILUHS Mk\WNVY3ODF{OES=
BON NVTQSlFVT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NXP2U2s4hjFy4pEK{txO MVXEUXNQ M1ixbGlEPTB;Nj62JO69VQ>? NVOzdnRzOTZ4MEGyPFQ>
CM NX;DR3JQT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MonxglXjiIsQvF2= MYHEUXNQ Ml;zTWM2OD1|LkOg{txO MXyxOlYxOTJ6NB?=
BON MXHGeY5kfGmxbjDhd5NigQ>? MnjZglcvPeLCit88US=> MnXnSG1UVw>? NFjLR5JqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0 MVOxOlYxOTJ6NB?=
CM M3vKUmZ2dmO2aX;uJIF{e2G7 Ml35glXjiIsQvF2= M1jIWGROW09? NE\HWVlqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0 MUmxOlYxOTJ6NB?=
BON MUnBdI9xfG:|aYOgZZN{[Xl? NV:0Uo1ChjdwNfMAju69VQ>? MX7EUXNQ M{nm[Ilv\HWlZYOgRZBweHSxc3nz M2DCNFE3PjBzMki0
CM MWPBdI9xfG:|aYOgZZN{[Xl? NGXIN2R,PeLCit88US=> NHHOSXlFVVOR MYPpcoR2[2W|IFHwc5B1d3Orcx?= NYnh[opuOTZ4MEGyPFQ>
HT-29 NH;sVmpIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MYn+NVDjiIsQvF2= MXHEUXNQ MXzJR|UxRTFwNzFOwG0> M4n2SFE4ODB5MEG1
HCT-116 NFHae4RIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NInxfGV,OTEkgJtOwG0> MUjEUXNQ NX;keXpKUUN3ME2yMlUh|ryP MojnNVcxODdyMUW=
primary colorectal cancer cells NHGyXm5HfW6ldHnvckBie3OjeR?= MmPuglXjiIsQvF2= MnzxSG1UVw>? MXfhcJRmenNidHjlJI1wenCqb3zv[5khd2ZidHjlJJJmdWGrbnnu[{Bk\Wyucx?= MYKxO|AxPzBzNR?=
HTLA-230 M3zwOWZ2dmO2aX;uJIF{e2G7 NVnaNopuhjhizszN MUPEUXNQ M2X3XYlvcGmkaYTzJGlITi2LST3t[YRq[XSnZDDzeIlufWyjdHnvckBw\iCLR1[tTXIh[W6mIFHreC=> NH\uVJgyPzF{MUi5PC=>
KCNR NUXaWJBVTnWwY4Tpc44h[XO|YYm= NH\PeWt,QCEQvF2= M4fiOWROW09? MVTpcohq[mm2czDJS2YuUUlvbXXkbYF1\WRic4TpcZVt[XSrb36gc4YhUUeILVnSJIFv\CCDa4S= M{DkXlE4OTJzOEm4
SK-N-BE2c NFvEXnRHfW6ldHnvckBie3OjeR?= MWf+PEDPxE1? NF7CZm9FVVOR NUXwRmtFcW6qaXLpeJMhUUeILVnJMY1m\GmjdHXkJJN1cW23bHH0bY9vKG:oIFnHSk1KWiCjbnSgRYt1 NYPHfGt6OTdzMkG4PVg>
SK-N-BE NVPFNIF3TnWwY4Tpc44h[XO|YYm= MkTqglgh|ryP MWLEUXNQ M4TBTIlvcGmkaYTzJGlITi2LST3t[YRq[XSnZDDzeIlufWyjdHnvckBw\iCLR1[tTXIh[W6mIFHreC=> NILmdFIyPzF{MUi5PC=>
LAN-5 NETqcY1HfW6ldHnvckBie3OjeR?= M4fCSZ45KM7:TR?= MVjEUXNQ NFjWZoNqdmirYnn0d{BKT0ZvSVmtcYVlcWG2ZXSgd5RqdXWuYYTpc44hd2ZiSVfGMWlTKGGwZDDBb5Q> MlTyNVcyOjF6OUi=
GI-CA-N MojaSpVv[3Srb36gZZN{[Xl? MmP0glgh|ryP MofPSG1UVw>? M2exNYlvcGmkaYTzJGlITi2LST3t[YRq[XSnZDDzeIlufWyjdHnvckBw\iCLR1[tTXIh[W6mIFHreC=> MX2xO|EzOTh7OB?=
SH-EP NHLkbI9HfW6ldHnvckBie3OjeR?= NI\iRnV,QCEQvF2= M3\zdmROW09? M4PjXYlvcGmkaYTzJGlITi2LST3t[YRq[XSnZDDzeIlufWyjdHnvckBw\iCLR1[tTXIh[W6mIFHreC=> M3LLWlE4OTJzOEm4
SK-N-AS NHjPbGlHfW6ldHnvckBie3OjeR?= NVnuZmFRhjhizszN M1zEVGROW09? NUfOVGRvcW6qaXLpeJMhUUeILVnJMY1m\GmjdHXkJJN1cW23bHH0bY9vKG:oIFnHSk1KWiCjbnSgRYt1 NV7CclgyOTdzMkG4PVg>
RN-GA M3n2XGZ2dmO2aX;uJIF{e2G7 MVH+PEDPxE1? NEHZW4ZFVVOR MnvibY5pcWKrdIOgTWdHNUmLLX3l[IlifGWmIIP0bY12dGG2aX;uJI9nKEmJRj3JVkBidmRiQXv0 MoPLNVcyOjF6OUi=
SY-5Y(N) NXrSUGFGTnWwY4Tpc44h[XO|YYm= MXT+PEDPxE1? NGi0[WJFVVOR NWryfpZTcW6qaXLpeJMhUUeILVnJMY1m\GmjdHXkJJN1cW23bHH0bY9vKG:oIFnHSk1KWiCjbnSgRYt1 NUe4T4ZvOTdzMkG4PVg>
GI-CA-N MkL0S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NXTkOpBihjhizszN M4nGSmROW09? MkXzTWM2OD1iNj64JO69VQ>? MWCxO|EzOTh7OB?=
SH-EP MYfHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NEjZcXV,QCEQvF2= NX21[nJRTE2VTx?= NHXsSlBKSzVyPTCzJO69VQ>? M1HxblE4OTJzOEm4
HTLA-230 NG\nbJVIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NGr6doR,QCEQvF2= NW\6ZXhOTE2VTx?= NGTVcXNKSzVyPTCwMlUh|ryP NHqye2UyPzF{MUi5PC=>
SK-N-BE2c MWfHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NIrhUmx,QCEQvF2= NX[3O3k4TE2VTx?= NELifXdKSzVyPTCxMlEh|ryP NGTLPW0yPzF{MUi5PC=>
SK-N-BE2 MkDJS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? Ml2yglgh|ryP MVrEUXNQ NFHFc3JKSzVyPTCzJO69VQ>? M3HDOFE4OTJzOEm4
SY-5Y (N) M4TDZmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MmX3glgh|ryP MmjPSG1UVw>? M1rXZ2lEPTB;IEKuOEDPxE1? M2TlWVE4OTJzOEm4
LAN-5 MVnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NH\Rc|B,QCEQvF2= MYfEUXNQ NGnkV3BKSzVyPTCwMlQh|ryP M2n5V|E4OTJzOEm4
KCNR MVzHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? M{H2Vp45KM7:TR?= Mo\ESG1UVw>? NGfqUllKSzVyPTCwMlQh|ryP NXK1cINpOTdzMkG4PVg>
RN-GA NVPSZ2tET3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= M33EVJ45KM7:TR?= NVHLe5c6TE2VTx?= M4DQcGlEPTB;IEGuN{DPxE1? Moj3NVcyOjF6OUi=
SK-N-AS MoflS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NYWzdWt7hjhizszN MlSySG1UVw>? MkT6bY5lfWOnczDhdI9xfG:|aYO= Mk\RNVcyOjF6OUi=
KCNR NXLEfmo4SXCxcITvd4l{KGG|c3H5 MWH+PEDPxE1? MYjEUXNQ MlrBbY5lfWOnczDhdI9xfG:|aYO= NIXUUoYyPzF{MUi5PC=>
GI-CA-N MofxRZBweHSxc3nzJIF{e2G7 NVjHWmtUhjhizszN MkP1SG1UVw>? MlLybY5lfWOnczDhdI9xfG:|aYO= NWP6fnBJOTdzMkG4PVg>
HTLA-230 NVPVT5luSXCxcITvd4l{KGG|c3H5 M1TFTJ45KM7:TR?= NETHTGpFVVOR MmjNbY5lfWOnczDhdI9xfG:|aYO= M37ZVlE4OTJzOEm4
SK-N-BE2c MYnBdI9xfG:|aYOgZZN{[Xl? MYL+PEDPxE1? NGS0RpZFVVOR NFG0PYdqdmS3Y3XzJIFxd3C2b4Ppdy=> NFHLOIQyPzF{MUi5PC=>
SY-5Y (N) MVzBdI9xfG:|aYOgZZN{[Xl? NGrxbFB,QCEQvF2= MkXLSG1UVw>? NEf3e2ZqdmS3Y3XzJIFxd3C2b4Ppdy=> NIXlfmYyPzF{MUi5PC=>
HL60AR MmntSpVv[3Srb36gZZN{[Xl? MlPNNVYxKG6P NXK0fo9T\W6qYX7j[ZMhfGinIHzleoVteyCxZjDwNldMcXBz M3izT|E4OzZzMkK1
HL60AR NF7kNohCeG:ydH;zbZMh[XO|YYm= NES3cnJ,OjByIH7N NWDlPXVYcW6mdXPld{BieG:ydH;zbZM> MkC4NVc{PjF{MkW=
HPAF-II NFroOXNMcW6jc3WgZZN{[Xl? MXn+NUDPxE1? M2XzbGROW09? Ml7xbY5pcWKrdIOgTWdHNUlvbXXkbYF1\WRic3nncoFtdGmwZx?= NVPNcZpDOTh2NEW1NlA>
HPAF-II NGDXdoZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NH\WcVR,OiEQvF2= NGrvVotFVVOR NVHpZVRVcW6qaXLpeJMh[2WubDDwdo9tcW[ncnH0bY9v M2naN|E5PDR3NUKw
HPAF-II NUnKdJlPTnWwY4Tpc44h[XO|YYm= NU\iUGJWhjJizszN NYPBU2FtTE2VTx?= NHfMcoVqdmirYnn0d{Bj[XOjbDDhcoQhUUeILVmtcYVlcWG2ZXSgdIFv[3KnYYTpZ{Bk[W6lZYKgZ4VtdCCvaXfyZZRqd25? NH[5bo0yQDR2NUWyNC=>
TFK-1 NVvjb4JvT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NFTESml,OjVyIH7N NWThWYV{TE2VTx?= M{TJSGlEPTB;MD6yOkDPxE1? NILUOXIzODB4NkezOC=>
EGI-1 Mm\GS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MYL+NlUxKG6P NF6zNnFFVVOR M2T5d2lEPTB;MD6yPEDPxE1? NXzMNG5MOjByNk[3N|Q>
CC-LP-1 NWHwVVlpT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MlLnglI2OCCwTR?= MWjEUXNQ M3v3NmlEPTB;MD6xOUDPxE1? M3rrVFIxODZ4N{O0
CC-SW-1 NWXXelh{T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= M3exOp4zPTBibl2= M2LjfWROW09? MWLJR|UxRTBwNUSg{txO NXrHZ4Q4OjByNk[3N|Q>
Sk-ChA-1 NGPQfmxIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MnzaglI2OCCwTR?= M3rxdGROW09? M3jYOGlEPTB;MD6yJO69VQ>? NIPLdngzODB4NkezOC=>
Mz-ChA-1 NGPMSYhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NH\QO5N,OjVyIH7N NWWzd4JuTE2VTx?= NX\2TlU{UUN3ME2xMlM6KM7:TR?= MnvUNlAxPjZ5M{S=
Mz-ChA-2 MlXUS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M2T2SJ4zPTBibl2= M4TM[WROW09? NUHlTHBPUUN3ME2wMlc{KM7:TR?= NF\USVYzODB4NkezOC=>
ECC-1 MYHLbY5ie2ViYYPzZZk> M{Hmep4yOCEQvF2= M2XmXWROW09? NYfvZW9wcW6qaXLpeJMhUUeILVnSJIFkfGm4YYTpc44h[nliOUil M4PWeFIyOjl3M{O1
Ishikawa MUXLbY5ie2ViYYPzZZk> NEX2Wnh,OTBizszN M2nvdWROW09? NXSwR|RrcW6qaXLpeJMhUUeILVnSJIFkfGm4YYTpc44h[nliOUOl MlTQNlEzQTV|M{W=
USPC-1 MULLbY5ie2ViYYPzZZk> M1XC[p4yOCEQvF2= Ml3PSG1UVw>? NHzXdmNqdmirYnn0d{BKT0ZvSWKgZYN1cX[jdHnvckBjgSBzMECl NIXqb20zOTJ7NUOzOS=>
USPC-2 NH7j[FNMcW6jc3WgZZN{[Xl? NF\QZYh,OTBizszN NFfPPHhFVVOR NV;3dIxrcW6qaXLpeJMhUUeILVnSJIFkfGm4YYTpc44h[nliOU[l MVqyNVI6PTN|NR?=
ECC-1 NXXIXmNVT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MV3+NVAh|ryP MnHQSG1UVw>? MUTk[YNz\WG|ZYOgZ4VtdCCycn;sbYZmemG2aX;u NY\H[4FZOjF{OUWzN|U>
Ishikawa MkPtS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MlraglExKM7:TR?= NWTuRVh6TE2VTx?= M4nUOoRm[3KnYYPld{Bk\WyuIIDyc4xq\mW{YYTpc44> NVvEdXRvOjF{OUWzN|U>
USPC-1 NED4NnRIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NHjkd4F,OTBizszN NIfWdGVFVVOR MnPB[IVkemWjc3XzJINmdGxicILvcIln\XKjdHnvci=> NW\ueFgyOjF{OUWzN|U>
USPC-2 MnrPS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MWD+NVAh|ryP NIqwUldFVVOR NFroW4Jl\WO{ZXHz[ZMh[2WubDDwdo9tcW[ncnH0bY9v NITifZQzOTJ7NUOzOS=>

... Click to View More Cell Line Experimental Data

In vivo NVP-AEW541 (50 mg/kg, p.o.) results in abrogation of basal and IGF-I-induced receptor, and PKB and MAPK phosphorylation, with T/C value of 14% in the NWT-21 tumor xenograft. [1] NVP-AEW541 (50 mg/kg) causes tumor shrinkage in both HTLA-230 and SK-N-BE2c xenografts, without signs of systemic toxicity. NVP-AEW541 could inhibit tumor invasion both in Matrigel-coated chambers and in HTLA-230 xenografts. [3]

Protocol

Kinase Assay:[1]
+ Expand

In vitro kinase assays:

NVP-AEW541 is dissolved in DMSO (10 mM) and stored at -20 °C. Dilutions are freshly made in DMSO/water 1:1. The final concentration of DMSO in the enzyme assays is <0.5 %. The protein kinase assays are carried out in 96-well plates at RT and terminated by the addition of 20 μL of 125 mM EDTA. Subsequently, 30 μL (c-Abl, c-Src, IGF-1R) of the reaction mixture are transferred onto Immobilon-PVDF presoaked for 5 min with methanol, rinsed with water, then soaked for 5 min with 0.5 % H3PO4 and mounted on vacuum manifold. After spotting all samples, vacuum is connected and each well rinsed with 200 μL 0.5 % H3PO4. Membranes are removed and washed 4× on a shaker with 1.0 % H3PO4, once with ethanol. After drying, mounting in Packard TopCount 96-well frame, and adding of 10 μL/well of Microscint, membranes are counted. IC50 values are calculated by linear regression analysis of the percentage inhibition of NVP-AEW541 in duplicate, at four concentrations (usually 0.01, 0.1, 1, and 10 μM). One unit of protein kinase activity is defined as 1 nmol of 33P transferred from [γ33P]ATP to the substrate protein per minute per mg of protein at 37 °C.
Cell Research:[1]
+ Expand
  • Cell lines: MCF-7 cells
  • Concentrations: ~ 10 μM
  • Incubation Time: 72 hours
  • Method: Between 3 × 103 and 6 × 103 cells/well are seeded in 96-well plates with a total media volume of 100 μL/well. Increasing concentrations of NVP-AEW541 is added 24 hours thereafter in quadruplicate. 72 hours later, cells are fixed by addition of 25 μL/well Glutaraldehyde (20%) and incubation for 10 min at RT. Cells are then washed 2× with 200 μL/well H2O and 100 μL Methylene Blue (0.05%) is added. After incubation for 10 min at RT, cells are washed 3× with 200 μL/well H2O. 200 μL/well HCl (3%) is added, and following incubation for 30 min at RT on a plate shaker, absorbance is measured at 650 nm.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Female Harlan athymic nude mice weighing 18-25 g with NWT-21 cells
  • Formulation: Dissolved in 25 mM L(+)-tartaric acid
  • Dosages: 20, 30, or 50 mg/kg
  • Administration: Administered via p.o. twice daily
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 88 mg/mL (200.2 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
20 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 439.55
Formula

C27H29N5O

CAS No. 475489-16-8
Storage powder
in solvent
Synonyms AEW541

Bio Calculators

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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IGF-1R Signaling Pathway Map

IGF-1R Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID