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NVP-AEW541 IGF-1R inhibitor

Name: NVP-AEW541
Brand: Selleck Chemicals
SKU: S1034
Availability: InStock
Rating: 5 (65 reviews)

Cat.No.S1034

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.

Chemical Structure

Molecular Weight: 439.55

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Quality Control

Batch: Purity: 99.61%

99.61

Related Targets	EGFR VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2
Other IGF-1R Inhibitors	Linsitinib (OSI-906) BMS-536924 BMS-754807 Picropodophyllin (AXL1717) GSK1904529A AG-1024 NVP-ADW742 NT157 PQ 401 Ginsenoside Rg5

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
NWT-21	Kinase assay	~10 μM		DMSO	inhibits IGF-IR with IC50 of 0.086 ± 0.028 μM	15050915
A14	Kinase assay	~10 μM		DMSO	inhibits InsR with IC50 of 2.3 ± 0.163 μM	15050915
A431	Kinase assay	~10 μM		DMSO	inhibits HER1 with IC50 of >10 μM	15050915
A31	Kinase assay	~10 μM		DMSO	inhibits PDGFR with IC50 of >10 μM	15050915
GIST882	Kinase assay	~10 μM		DMSO	inhibits c-Kit with IC50 of >5 μM	15050915
32D-Bcr-Abl	Kinase assay	~10 μM		DMSO	inhibits Bcr-Abl p210 with IC50 of >10 μM	15050915
MCF-7	Cytoxicity assay			DMSO	IC50=1.64 μM	15050915
NWT-21	Growth inhibitory assay			DMSO	IC50=0.163 μM	15050915
TC-71	Growth inhibitory assay	~1 μM		DMSO	inhibits insulin-like growth factor-I–mediated growth	15867386
TC-71	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
Saos-2	Growth inhibitory assay	~7 μM		DMSO	IC50<3 μM	15867386
U-2OS	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
SK-ES-1	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
SK-N-MC	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
RD-ES	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
SJ-Rh 30	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
SJ-Rh 4	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
6647	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
SARG	Growth inhibitory assay	~7 μM		DMSO	IC50<3 μM	15867386
MOS	Growth inhibitory assay	~7 μM		DMSO	IC50<4 μM	15867386
IOR/OS7	Growth inhibitory assay	~7 μM		DMSO	IC50<1 μM	15867386
IOR/OS9	Growth inhibitory assay	~7 μM		DMSO	IC50<6 μM	15867386
IOR/OS10	Growth inhibitory assay	~7 μM		DMSO	IC50<5 μM	15867386
IOR/OS14	Growth inhibitory assay	~7 μM		DMSO	IC50<4 μM	15867386
LAP35	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
IOR/BRZ	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
IOR/CAR	Growth inhibitory assay	~7 μM		DMSO	IC50<1 μM	15867386
IOR/NGR	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
IOR/RCH	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
RMZ-RC2	Growth inhibitory assay	~7 μM		DMSO	IC50<0.5 μM	15867386
CCA	Growth inhibitory assay	~7 μM		DMSO	IC50<2 μM	15867386
RD/18	Growth inhibitory assay	~7 μM		DMSO	IC50<4 μM	15867386
OVCAR-3	Growth inhibitory assay	~15 μM		DMSO	inhibits cell proliferation	16300820
OVCAR-4	Growth inhibitory assay	~15 μM		DMSO	inhibits cell proliferation	16300820
OVCAR-3	Apoptosis assay	~15 μM		DMSO	induces apoptosis	16300820
OVCAR-4	Apoptosis assay	~15 μM		DMSO	induces apoptosis	16300820
OVCAR-3	Function assay	~15 μM		DMSO	Decreases phosphorylation of AKT	16300820
Huh-7	Growth inhibitory assay	~10 μM		DMSO	IC50=1.4 μM	16530734
Hep-G2	Growth inhibitory assay	~10 μM		DMSO	IC50=1.8 μM	16530734
Hep-3B	Growth inhibitory assay	~10 μM		DMSO	IC50=1.9 μM	16530734
SK-Hep-1	Growth inhibitory assay	~10 μM		DMSO	IC50=6.9 μM	16530734
Huh-7	Function assay	~10 μM		DMSO	Induces cell cycle arrest	16530734
Hep-G2	Function assay	~10 μM		DMSO	Induces cell cycle arrest	16530734
SK-Hep-1	Function assay	~10 μM		DMSO	Induces cell cycle arrest	16530734
BON	Kinase assay	~6 μM		DMSO	induces dephosphorylation of IGF-1R	16601284
BON	Growth inhibitory assay	~10 μM		DMSO	IC50=6.6 μM	16601284
CM	Growth inhibitory assay	~5 μM		DMSO	IC50=3.3 μM	16601284
BON	Function assay	~7.5 μM		DMSO	induces cell cycle arrest	16601284
CM	Function assay	~5 μM		DMSO	induces cell cycle arrest	16601284
BON	Apoptosis assay	~7.5 μM		DMSO	induces Apoptosis	16601284
CM	Apoptosis assay	~5 μM		DMSO	induces Apoptosis	16601284
HT-29	Growth inhibitory assay	~10 μM		DMSO	IC50=1.7 μM	17007015
HCT-116	Growth inhibitory assay	~10 μM		DMSO	IC50=2.5 μM	17007015
primary colorectal cancer cells	Function assay	~5 μM		DMSO	alters the morphology of the remaining cells	17007015
HTLA-230	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
KCNR	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
SK-N-BE2c	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
SK-N-BE	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
LAN-5	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
GI-CA-N	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
SH-EP	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
SK-N-AS	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
RN-GA	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
SY-5Y(N)	Function assay	~8 μM		DMSO	inhibits IGF-II-mediated stimulation of IGF-IR and Akt	17121898
GI-CA-N	Growth inhibitory assay	~8 μM		DMSO	IC50= 6.8 μM	17121898
SH-EP	Growth inhibitory assay	~8 μM		DMSO	IC50= 3 μM	17121898
HTLA-230	Growth inhibitory assay	~8 μM		DMSO	IC50= 0.5 μM	17121898
SK-N-BE2c	Growth inhibitory assay	~8 μM		DMSO	IC50= 1.1 μM	17121898
SK-N-BE2	Growth inhibitory assay	~8 μM		DMSO	IC50= 3 μM	17121898
SY-5Y (N)	Growth inhibitory assay	~8 μM		DMSO	IC50= 2.4 μM	17121898
LAN-5	Growth inhibitory assay	~8 μM		DMSO	IC50= 0.4 μM	17121898
KCNR	Growth inhibitory assay	~8 μM		DMSO	IC50= 0.4 μM	17121898
RN-GA	Growth inhibitory assay	~8 μM		DMSO	IC50= 1.3 μM	17121898
SK-N-AS	Growth inhibitory assay	~8 μM		DMSO	induces apoptosis	17121898
KCNR	Apoptosis assay	~8 μM		DMSO	induces apoptosis	17121898
GI-CA-N	Apoptosis assay	~8 μM		DMSO	induces apoptosis	17121898
HTLA-230	Apoptosis assay	~8 μM		DMSO	induces apoptosis	17121898
SK-N-BE2c	Apoptosis assay	~8 μM		DMSO	induces apoptosis	17121898
SY-5Y (N)	Apoptosis assay	~8 μM		DMSO	induces apoptosis	17121898
HL60AR	Function assay	160 nM			enhances the levels of p27Kip1	17361225
HL60AR	Apoptosis assay	~200 nM			induces apoptosis	17361225
HPAF-II	Kinase assay	~1 μM		DMSO	inhibits IGF-I-mediated signalling	18445520
HPAF-II	Growth inhibitory assay	~2 μM		DMSO	inhibits cell proliferation	18445520
HPAF-II	Function assay	~2 μM		DMSO	inhibits basal and IGF-I-mediated pancreatic cancer cell migration	18445520
TFK-1	Growth inhibitory assay	~250 nM		DMSO	IC50=0.26 μM	20066734
EGI-1	Growth inhibitory assay	~250 nM		DMSO	IC50=0.28 μM	20066734
CC-LP-1	Growth inhibitory assay	~250 nM		DMSO	IC50=0.15 μM	20066734
CC-SW-1	Growth inhibitory assay	~250 nM		DMSO	IC50=0.54 μM	20066734
Sk-ChA-1	Growth inhibitory assay	~250 nM		DMSO	IC50=0.2 μM	20066734
Mz-ChA-1	Growth inhibitory assay	~250 nM		DMSO	IC50=1.39 μM	20066734
Mz-ChA-2	Growth inhibitory assay	~250 nM		DMSO	IC50=0.73 μM	20066734
ECC-1	Kinase assay	~10 μM		DMSO	inhibits IGF-IR activation by 98%	21295335
Ishikawa	Kinase assay	~10 μM		DMSO	inhibits IGF-IR activation by 93%	21295335
USPC-1	Kinase assay	~10 μM		DMSO	inhibits IGF-IR activation by 100%	21295335
USPC-2	Kinase assay	~10 μM		DMSO	inhibits IGF-IR activation by 96%	21295335
ECC-1	Growth inhibitory assay	~10 μM		DMSO	decreases cell proliferation	21295335
Ishikawa	Growth inhibitory assay	~10 μM		DMSO	decreases cell proliferation	21295335
USPC-1	Growth inhibitory assay	~10 μM		DMSO	decreases cell proliferation	21295335
USPC-2	Growth inhibitory assay	~10 μM		DMSO	decreases cell proliferation	21295335
Ba/F3	Function assay				Inhibition of full length IGF-1 receptor (unknown origin) transfected in Ba/F3 cells assessed as cell proliferation, IC50=0.02μM	26951753
HEK293	Function assay		60 mins		Inhibition of full length IGF-1 receptor (unknown origin) autophosphorylation transfected in HEK293 cells pretreated for 60 mins followed by IGF-1 stimulation measured after 10 mins by quantitative Western blot analysis, IC50=0.065μM	26951753
HEK293	Function assay				Displacement of [3H]-dofetilide from human ERG channel expressed in HEK293 cells, IC50=0.13μM	26951753
Ba/F3	Function assay				Inhibition of full length insulin receptor (unknown origin) transfected in Ba/F3 cells assessed as cell proliferation, IC50=0.244μM	26951753
HEK293	Function assay		60 mins		Inhibition of full length insulin receptor (unknown origin) autophosphorylation transfected in HEK293 cells pretreated for 60 mins followed by IGF-1 stimulation measured after 10 mins by quantitative Western blot analysis, IC50=0.892μM	26951753
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 88 mg/mL (200.2 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 24 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%PEG400 1 0.5%Tween80 2 5%propylene glycol Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	20.000mg/ml (45.50mM)	Taking the 1 mL working solution as an example, add 300 μL of clarified PEG400 stock solution of 66.67 mg/ml to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O Dilute to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Average weight of animals: g

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	439.55	Formula	C₂₇H₂₉N₅O	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	475489-16-8	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	AEW541			Smiles	C1CN(C1)CC2CC(C2)N3C=C(C4=C(N=CN=C43)N)C5=CC(=CC=C5)OCC6=CC=CC=C6

Mechanism of Action

Targets/IC₅₀/Ki	Insulin Receptor (Cell-free assay) 0.14 μM IGF-1R (Cell-free assay) 0.15 μM FLT3 (Cell-free assay) 0.42 μM Tek (Cell-free assay) 0.53 μM FLT1 (Cell-free assay) 0.6 μM HER4 (Cell-free assay) 1.4 μM PDGFR (Cell-free assay) 2.0 μM KDR (Cell-free assay) 2.3 μM c-Src (Cell-free assay) 2.4 μM FLT4 (Cell-free assay) 2.4 μM c-Kit (Cell-free assay) 3.3 μM c-Met (Cell-free assay) 3.8 μM HER2 (Cell-free assay) 4.1 μM FGFR1 (Cell-free assay) 4.1 μM PDK-1 (Cell-free assay) 4.8 μM HER1 (Cell-free assay) 5.8 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. This compound is more selective and shows 27-fold more potent than InsR at the cellular level. It 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. This chemical also reduces the level of phospho-IGF-1R and phospho-PKB in NWT-21 cells. It shows growth inhibitory effect on TC-71 musculoskeletal sarcoma cells in low-serum medium as well as in 10% FBS–containing medium. This compound inhibits cell cycle progression and induces specific G1 arrest in sarcoma cell lines (TC-71, SK-N-MC, SaoS-2, RD/18 and RH4). It 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. This compound-driven inhibition of IGF-1R causes a reduction of phosphorylation of Akt, but not of Erk1 and Erk2 in neuroblastoma cells. It inhibits glioma cell growth and disrupts the autocrine loop initiated by HIF1α stabilization. A recent study shows that this chemical suppresses the proliferation and viability of PC3, DU145, and 22Rv1 prostate cancer cells, without necessarity of associated cell death. It 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 this compound with essential Akt. This compound-induced radiosensization is dependent on Akt activation status. It could increase the H2AX phosphorylation (a measure of DSBs) in PC3, DU145, and 22Rv1 cells.
Kinase Assay	In vitro kinase assays
Kinase Assay	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 this compound 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.
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. This compound (50 mg/kg) causes tumor shrinkage in both HTLA-230 and SK-N-BE2c xenografts, without signs of systemic toxicity. It could inhibit tumor invasion both in Matrigel-coated chambers and in HTLA-230 xenografts.
References	[1] https://pubmed.ncbi.nlm.nih.gov/15050915/ [2] https://pubmed.ncbi.nlm.nih.gov/15867386/ [3] https://pubmed.ncbi.nlm.nih.gov/17121898/ [4] https://pubmed.ncbi.nlm.nih.gov/20488164/ [5] http://www.ncbi.nlm.nih.gov/m/pubmed/21816290/

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