| Size | Price | |
|---|---|---|
| 50mg | ||
| 100mg | ||
| 250mg | ||
| 500mg | ||
| Other Sizes |
Purity: ≥98%
NVP-AEW541 (also known as AEW541; AEW-541) is a novel, potent and selective inhibitor of IGF-1R/InsR with potential antineoplastic activity. In cell-free assays, it inhibits IGF-1R/InsR with IC50s of 150 nM/140 nM. In a cell-based assay, NVP-AEW541 exhibits higher potency and selectivity for IGF-1R. In soft agar, NVP-AEW541 blocks IGF-I-mediated survival and colony formation at levels that are compatible with suppressing IGF-IR autophosphorylation. This oral bioavailable substance considerably slows the growth of IGF-IR-driven fibrosarcomas and inhibits IGF-IR signaling in tumor xenografts in vivo. As a result, NVP-AEW541 is a member of a class of small, selective IGF-IR kinase inhibitors that have demonstrated in vivo antitumor activity and may find use in therapeutic settings.
| Targets |
Insulin Receptor (IC50 = 0.14 μM); IGF-1R (IC50 = 0.15 μM); FLT3 (IC50 = 0.42 μM); Tek (IC50 = 0.53 μM); FLT1 (IC50 = 0.6 μM)
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| ln Vitro |
NVP-AEW541 also inhibits InsR, Tek, Flt1 and Flt3 in the purified kinases/recombinant kinase domains assay, with IC50 values of 140 nM, 530 nM, 600 nM, and 420 nM. At the cellular level, NVP-AEW541 is 27 times more potent and more selective than InsR. NVP-AEW541 inhibits MCF-7 cells' IGF-I-mediated survival, soft agar, and proliferation, with IC50 values of 0.162 μM, 0.105 μM, and 1.64 μM, in that order. In NWT-21 cells, NVP-AEW541 also lowers the levels of phospho-PKB and phospho-IGF-1R.[1] NVP-AEW541 inhibits the growth of TC-71 musculoskeletal sarcoma cells in both 10% FBS-containing medium and low-serum medium. In sarcoma cell lines, NVP-AEW541 inhibits the progression of the cell cycle and causes a particular G1 arrest (TC-71, SK-N-MC, SaoS-2, RD/18 and RH4).[2] With an IC50 of 0.4-6.8 μM, NVP-AEW541 may be able to stop human neuroblastoma cell growth. These cell lines showed a decrease in the S and G2-M compartments as well as an increase in the hypodiploid fraction. In neuroblastoma cells, NVP-AEW541-driven inhibition of IGF-1R reduces Akt phosphorylation but not Erk1 or Erk2.[3] Glioma cell growth is suppressed by NVP-AEW541, which also breaks the autocrine loop that is started by HIF1α stabilization.[4] According to a recent study, NVP-AEW541 inhibits the growth and survival of PC3, DU145, and 22Rv1 prostate cancer cells without necessarily causing corresponding cell death. While NVP-AEW541 has no effect on total Akt levels, it lowers phospho-Akt levels in PC3 cells but not in 22Rv1 or DU415 cells. This suggests that the effectiveness of NVP-AEW541 with essential Akt may depend on PTEN status. The level of Akt activation determines whether NVP-AEW541-induced radiosensization occurs. In PC3, DU145, and 22Rv1 cells, NVP-AEW541 may raise H2AX phosphorylation, a marker of DSBs.[5]
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| ln Vivo |
NVP-AEW541 causes the NWT-21 tumor xenograft's T/C value to be 14%, abrogating the phosphorylation of PKB and MAPK as well as the basal and IGF-I-induced receptors. (Source: ) Without exhibiting any symptoms of systemic toxicity, NVP-AEW541 (50 mg/kg) shrinks tumors in HTLA-230 and SK-N-BE2c xenografts. Matrigel-coated chambers and HTLA-230 xenografts were two environments in which NVP-AEW541 could prevent tumor invasion.[3]
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| Enzyme Assay |
NVP-AEW541 is kept at -20 °C after being dissolved in 10 mM DMSO. Fresh dilutions are made using a 1:1 DMSO/water ratio. In the enzyme tests, the final DMSO concentration is less than 0.5%. In 96-well plates, the protein kinase assays are conducted at room temperature and are finished with the addition of 20 μL of 125 mM EDTA. Next, 30 μL of the reaction mixture (c-Abl, c-Src, and IGF-1R) are placed onto Immobilon-PVDF. mounted on a vacuum manifold after being presoaked in methanol for five minutes, rinsed with water, and soaked in 0.5% H3PO4 for five minutes. Once every sample has been spotted, the vacuum is connected, and 200 μL of 0.5% H3PO4 is rinsed through each well. The membranes are taken out and cleaned four times on a shaker using 1% H3PO4 and ethanol. Membranes are counted following drying, mounting in a Packard TopCount 96-well frame, and the addition of 10 μL/well of Microscint. The percentage inhibition of NVP-AEW541 at four concentrations (typically 0.01, 0.1, 1, and 10 μM) is subjected to a linear regression analysis to determine the IC50 values. A single unit of protein kinase activity is measured as one nanomol of 33P transferred per minute per milligram of protein at 37°C from [γ33P]ATP to the substrate protein.
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| Cell Assay |
In 96-well plates, 3 × 103 to 6 × 103 cells/well are seeded with a 100 μL media volume per well. Twenty-four hours later, quadruplicate doses of NVP-AEW541 are added. The cells are fixed 72 hours later by adding 25 μL/well of 20% glutaraldehyde and letting them sit at room temperature for 10 minutes. After two rounds of washing with 200 μL/well H2O, 100 μL of Methylene Blue (0.05%) is added to the cells. Cells are washed three times with 200 μL/well H2O following a 10-minute incubation period at room temperature. After adding 200 μL/well of HCl (3%) and incubating on a plate shaker for 30 minutes at room temperature, absorbance at 650 nm is measured.
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| Animal Protocol |
Female Harlan athymic nude mice weighing 18-25 g with NWT-21 cells
20, 30, or 50 mg/kg Administered via p.o. twice daily |
| References |
| Molecular Formula |
C27H29N5O
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|---|---|
| Molecular Weight |
439.55
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| Exact Mass |
439.237
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| CAS # |
475488-34-7
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| Related CAS # |
475488-34-7; 1618643-96-1 (HCl); 475489-16-8 (cis-isomer free base); 2320261-63-8 (cis-isomer HCl)
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| PubChem CID |
11476171
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
5.435
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
632
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)COC2=CC=CC(=C2)C3=CN([C@H]4C[C@@H](C4)CN5CCC5)C6=NC=NC(=C36)N
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| InChi Key |
AECDBHGVIIRMOI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H29N5O/c28-26-25-24(21-8-4-9-23(14-21)33-17-19-6-2-1-3-7-19)16-32(27(25)30-18-29-26)22-12-20(13-22)15-31-10-5-11-31/h1-4,6-9,14,16,18,20,22H,5,10-13,15,17H2,(H2,28,29,30)
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| Chemical Name |
7-[3-(azetidin-1-ylmethyl)cyclobutyl]-5-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine
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| Synonyms |
AEW 541; AEW541; NVP-AEW541; NVP-AEW 541; NVP-AEW-541; AEW-541
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 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 | |
| 10 mM | 0.2275 mL | 1.1375 mL | 2.2751 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NVP-AEW541 inhibits tumor growth in neuroblastoma xenografts. Clin Cancer Res. 2006 Nov 15;12(22):6772-80. |
NVP-AEW541 inhibits tumor invasion in Matrigel-coated chambers. Clin Cancer Res. 2006 Nov 15;12(22):6772-80. |
NVP-AEW541 inhibits tumor invasion in vivo. Clin Cancer Res. 2006 Nov 15;12(22):6772-80. |
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