NVP-AEW541

製品コードS1034 バッチS103403

印刷

化学情報

Chemical Structure Synonyms AEW541 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H29N5O
分子量 439.55 CAS No. 475489-16-8
Solubility (25°C)* 体外 DMSO 88 mg/mL (200.2 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
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.
* <1 mg/ml means slightly soluble or insoluble.
* 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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. [1] 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). [2] 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. [3] It inhibits glioma cell growth and disrupts the autocrine loop initiated by HIF1α stabilization. [4] 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. [5]
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] 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. [3]

プロトコル(参考用のみ)

キナーゼアッセイ 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 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.
細胞アッセイ 細胞株 MCF-7 cells
濃度 ~ 10 μM
反応時間 72 hours
実験の流れ 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 this compound 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.
動物実験 動物モデル Female Harlan athymic nude mice weighing 18-25 g with NWT-21 cells
投薬量 20, 30, or 50 mg/kg
投与方法 Administered via p.o. twice daily

参考

  • https://pubmed.ncbi.nlm.nih.gov/15050915/
  • https://pubmed.ncbi.nlm.nih.gov/15867386/
  • https://pubmed.ncbi.nlm.nih.gov/17121898/
  • https://pubmed.ncbi.nlm.nih.gov/20488164/
  • http://www.ncbi.nlm.nih.gov/m/pubmed/21816290/

カスタマーフィードバック

Data from [Data independently produced by Breast Cancer Res, 2013, 15, R55]

Data from [J Clin Invest, 2011, 121, 4311-21]

Data from [Clin Cancer Res, 2011, 17, 2237-2249]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Translocation of IGF-1R in endoplasmic reticulum enhances SERCA2 activity to trigger Ca2+ER perturbation in hepatocellular carcinoma [ Acta Pharm Sin B, 2023, 13(9):3744-3755] PubMed: 37719369
Translocation of IGF-1R in endoplasmic reticulum enhances SERCA2 activity to trigger Ca2+ER perturbation in hepatocellular carcinoma [ Acta Pharm Sin B, 2023, 13(9):3744-3755] PubMed: 37719369
Anatomic position determines oncogenic specificity in melanoma [ Nature, 2022, 604(7905):354-361] PubMed: 35355015
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
SFRP4+ stromal cell subpopulation with IGF1 signaling in human endometrial regeneration [ Cell Discov, 2022, 8(1):95] PubMed: 36163341
Comprehensive drug response profiling and pan-omic analysis identified therapeutic candidates and prognostic biomarkers for Asian cholangiocarcinoma [ iScience, 2022, 25(10):105182] PubMed: 36248745
Strong Synergic Growth Inhibition and Death Induction of Cancer Cells by Astragalus membranaceus and Vaccaria hispanica Extract [ Cancers (Basel), 2022, 14(23)5833] PubMed: 36497315
Differential cytotoxic activity of pharmacological inhibitors of IGF1R-related pathways in JAK2V617F driven cells [ Toxicol In Vitro, 2022, 83:105384] PubMed: 35568132
Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis [ Cancer Cell, 2021, S1535-6108(21)00383-4] PubMed: 34388376
Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms [ Cancer Cell, 2021, S1535-6108(21)00492-X] PubMed: 34624218

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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