NVP-AEW541 (Synonyms: AEW541) |
| Catalog No.GC12963 |
IGF-IR inhibitor, novel, potent and selective
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 475489-16-8
Sample solution is provided at 25 µL, 10mM.
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NVP-AEW541 is a novel, potent and selective inhibitor of IGF-IR kinase with IC50 value of 0.086 μM [1].
NVP-AEW541 is a pyrrolo(2,3-d) pyrimidine derivative. It has been reported to abolish IGF-I-induced IGF-IR autophosphorylation and to block the IGF-IR signaling pathway mainly in ECC-1 and USPC-1 cancer cells. Also in these cell lines, NVP-AEW541 has been shown to change the IGF-I induced cell cycle and to lead apoptotic cell death as well as exhibit antiproliferative effects [2]. In addition, it is observed that NVP-AEW541 can induce radiosensitization in PTEN wild-type cell lines [3].
Reference:
[1] Carlos Garc a-Echeverr a, Mark A. Pearson, Andreas Marti, Thomas Meyer, Juergen Mestan, Johann Zimmermann, Jiaping Gao, Josef Brueggen, Hans-Georg Capraro, Robert Cozens, Dean B. Evans, Doriano Fabbro, Pascal Furet, Diana Graus Porta, Janis Liebetanz, Georg Martiny-Baron, Stephan Ruetz, and Francesco Hofmann. In vivo antitumor activity of NVP-AEW541—A novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell.2004 Mar (5):231-239.
[2] Zohar Attias-Geva, Itay Bentov, Ami Fishman, Haim Werner, Ilan Bruchim. Insulin-like growth factor-I receptor inhibition by speci c tyrosine kinase inhibitor NVP-AEW541 in endometrioid and serous papillary endometrial cancer cell lines. Gynecologic Oncology. 2011 Feb (121):383-389.
[3] Sofie F. Isebaert, Johannes V. Swinnen, William H. Mcbride, and Karin M. Haustermans. Insulin-like growth factor–type 1 receptor inhibitor NVP-AEW541 enhances radiosensitivity of PTEN wild-type but not PTEN-deficient human prostate cancer cells. International Journal of Radiation Oncology Biology Physics. 2011 (81):239-247.
| Kinase experiment [1]: | |
|
In vitro kinase assays |
NVP-AEW541 was dissolved in DMSO (10 mM) and stored at -20°C. Dilutions were freshly made in DMSO/water 1:1. The final concentration of DMSO in the enzyme assays was < 0.5 %. The protein kinase assays were 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 were transferred onto Immobilon-PVDF presoaked for 5 mins with methanol, rinsed with water, then soaked for 5 mins with 0.5 % H3PO4 and mounted on vacuum manifold. After spotting all samples, vacuum was connected and each well rinsed with 200 μL 0.5 % H3PO4. Membranes were removed and washed 4 times 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 were counted. The IC50 values were calculated by linear regression analysis of the percentage inhibition of NVP-AEW541 in duplicate, at 4 concentrations (usually 0.01, 0.1, 1, and 10 μM). One unit of protein kinase activity was defined as 1 nmol of 33P transferred from [γ33P]ATP to the substrate protein per minute per mg of protein at 37°C. |
| Cell experiment [1]: | |
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Cell lines |
MCF-7 cells |
|
Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reaction Conditions |
~ 10 μM; 72 hrs |
|
Applications |
In MCF-7 cells, NVP-AEW541 suppressed the IGF-I-mediated survival, soft agar and cell proliferation with IC50 values of 0.162 μM, 0.105 μM and 1.64 μM, respectively. |
| Animal experiment [1]: | |
|
Animal models |
Female Harlan athymic nude mice with NWT-21 cells |
|
Dosage form |
20, 30, or 50 mg/kg; p.o.; twice daily, 7 days/week |
|
Applications |
NVP-AEW541 dose-dependently inhibited tumor growth with T/C values of 32%, 28% and 14% at the doses of 20 mg, 30 mg, or 50 mg, respectively. NVP-AEW541 was well tolerated at the indicated doses, and the recorded variations in body weight were not statistically significant. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. García-Echeverría C, Pearson MA, Marti A, et al. In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell, 2004, 5(3): 231-239. | |
| Cas No. | 475489-16-8 | SDF | |
| Synonyms | AEW541 | ||
| Chemical Name | 7-[3-(azetidin-1-ylmethyl)cyclobutyl]-5-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine | ||
| Canonical SMILES | C1CN(C1)CC2CC(C2)N3C=C(C4=C3N=CN=C4N)C5=CC(=CC=C5)OCC6=CC=CC=C6 | ||
| Formula | C27H29N5O | M.Wt | 439.55 |
| Solubility | ≥ 22mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2751 mL | 11.3753 mL | 22.7505 mL |
| 5 mM | 0.455 mL | 2.2751 mL | 4.5501 mL |
| 10 mM | 0.2275 mL | 1.1375 mL | 2.2751 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)
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