1. Protein Tyrosine Kinase/RTK Autophagy
  2. IGF-1R Insulin Receptor Autophagy
  3. NVP-AEW541

NVP-AEW541 (AEW541 ) is an orally active inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with an IC50 value of 0.15 μM. NVP-AEW541 also inhibits InsR, IC50 with a value of 0.14 μM. NVP-AEW541 has antitumor activity.

For research use only. We do not sell to patients.

NVP-AEW541 Chemical Structure

NVP-AEW541 Chemical Structure

CAS No. : 475489-16-8

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 132 In-stock
Solution
10 mM * 1 mL in DMSO USD 132 In-stock
Solid
5 mg USD 120 In-stock
10 mg USD 190 In-stock
50 mg USD 590 In-stock
100 mg USD 950 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 6 publication(s) in Google Scholar

Other Forms of NVP-AEW541:

Top Publications Citing Use of Products
  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

NVP-AEW541 (AEW541 ) is an orally active inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with an IC50 value of 0.15 μM. NVP-AEW541 also inhibits InsR, IC50 with a value of 0.14 μM. NVP-AEW541 has antitumor activity[1].

IC50 & Target

IC50: 0.15 ±0.036 μM (IGF-IR), 0.14±0.039 μM (InsR), 0.42±0.11 μM (Flt-3), 2±0.61 μM (PDGFR), 2.4±0.38 μM (c-Src), 3.3±1.4 μM (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 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[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

439.55

Formula

C27H29N5O

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

NC1=C2C(N([C@@H]3C[C@@H](C3)CN4CCC4)C=C2C5=CC=CC(OCC6=CC=CC=C6)=C5)=NC=N1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 50 mg/mL (113.75 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.2751 mL 11.3753 mL 22.7505 mL
5 mM 0.4550 mL 2.2751 mL 4.5501 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (5.69 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: 2.5 mg/mL (5.69 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
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+
%
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%
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: ≥99.0%

References
Kinase Assay
[1]

The activities of protein kinases are assayed in the presence or absence of inhibitors by measuring the incorporation of 33P from [γ33P]ATP (1000 Ci/mmol) into appropriate substrates. The protein kinase assays are carried out in 96-well plates at RT under conditions described in details below andterminated by the addition of 20 μL of 125 mM EDTA. Subsequently, 30 μL (c-Abl, c-Src, IGF-1R) or 40 μL (all other kinases) of the reaction mixture are transferred onto Immobilon-PVDF pre-soaked 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% 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 each 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 nmole of 33P transferred from [γ33P]ATP to the substrate protein per minute per mg of protein at 37C[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

Between 3000 and 6000 cells/well are seeded in 96-well plates with a total media volume of 100 μL/well. Increasing concentrations of the compound are added 24 hr thereafter in quadruplicate. 72 hr 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 200μL/well H2O and 100μL 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[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Mice[1]
Female Harlan athymic nude mice are used NWT-21 cells are grown in DMEM (high glucose, 4.5 g/L), 10% FCS, 1% L-glutamine, and 1% Na-pyruvate. 5×106 cells/animal are initially injected s.c. into the right flank of five mice. For the in vivo efficacy experiment, tumors of 500 to 800 mm3 are excised and nonnecrotic areas are cut to fragments of 3×3×3 mm. Tumor fragments are washed in sterile PBS and one tumor fragment per animal is trans- planted s.c. into the right flank. Tumor volumes (length×width ×height×π/6) and body weights are determined three times weekly. At the first day of treatment (day 0), the therapy group (NVP-AEW541) and the control group (vehicle only) are selected by stratification (8 animals per group, average tumor volume of about 95 mm3 per group). Animals are treated p.o. twice daily, 7 days/week either with NVP-AEW541 (20, 30, or 50 mg/kg; 10 mL/kg dissolved in 25 mM L(+)-tartaric acid, therapy group) or with 25 mM L(+)-tartaric acid (control group). Antitumor activity is expressed as T/C%(mean increase of tumor volumes of treated animals divided by the mean increase of tumor volumes of control animals multiplied by 100). The experiment is terminated when the mean tumor volume is about 1500 mm3.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.2751 mL 11.3753 mL 22.7505 mL 56.8764 mL
5 mM 0.4550 mL 2.2751 mL 4.5501 mL 11.3753 mL
10 mM 0.2275 mL 1.1375 mL 2.2751 mL 5.6876 mL
15 mM 0.1517 mL 0.7584 mL 1.5167 mL 3.7918 mL
20 mM 0.1138 mL 0.5688 mL 1.1375 mL 2.8438 mL
25 mM 0.0910 mL 0.4550 mL 0.9100 mL 2.2751 mL
30 mM 0.0758 mL 0.3792 mL 0.7584 mL 1.8959 mL
40 mM 0.0569 mL 0.2844 mL 0.5688 mL 1.4219 mL
50 mM 0.0455 mL 0.2275 mL 0.4550 mL 1.1375 mL
60 mM 0.0379 mL 0.1896 mL 0.3792 mL 0.9479 mL
80 mM 0.0284 mL 0.1422 mL 0.2844 mL 0.7110 mL
100 mM 0.0228 mL 0.1138 mL 0.2275 mL 0.5688 mL
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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