受注:045-509-1970 |
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Synonyms | Tyrphostin, AGS 200 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C14H13BrN2O |
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分子量 | 305.17 | CAS No. | 65678-07-1 | ||||
Solubility (25°C)* | 体外 | DMSO | 61 mg/mL (199.88 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) |
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* <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. |
製品説明 | AG-1024 (Tyrphostin, AGS 200) inhibits IGF-1R autophosphorylation with IC50 of 7 μM, is less potent to IR with IC50 of 57 μM and specifically distinguishes between InsR and IGF-1R (as compared to other tyrphostins). |
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in vitro | AG-1024 blocks the IGF-1 receptor and IR autophosphorylation with IC50 of 7 μM and 57 μM, respectively. AG-1024 also inhibits the receptor tyrosine kinase activity towards exogenous substrates (TKA) with IC50 values of 18 μM and 80 μM, respectively. [1] AG-1024 (10 μM) inhibits cell proliferation in a time-dependent manner, and induces apoptosis in MCF-7 cells at 48 hours by 20.1% and >40% when combined with irradiation (10 Gy), more potently than that of irradiation (10 Gy) alone by 11.8%, which is associated with a down-regulation of phospho-Akt1 and bcl-2, and up-regulation of Bax, p53 and p21. [2] AG-1024 significantly inhibits melanoma cell proliferation with an IC50 of <50 nM in the absence of serum, by blocking MAPK/ERK2 signaling, subsequently rapidly inducing pRb dephosphorylation and activation, and eventually the formation of growth suppressive pRb-E2F complexes. [3] AG-1024 treatment down-regulates the expression of Bcr-Abl and P-Akt, and up-regulates DNA-PKcs expression in UT7-9 and Ba/F3-p210 cells, leading to decreased clonogenic survival and proliferation. AG-1024 also significantly inhibits the proliferation of cells resistant to the BCR-ABL inhibitor STI571, which correlates with a dose-dependent decrease in Bcr-Abl protein expression. [4] |
in vivo | Administration of AG-1024 at a dose of 30 μg for 10 days significantly inhibits the tumor growth of Ba/F3-p210 xenograft in mice. [4] |
キナーゼアッセイ | Inhibition of IGF-1- and insulin-stimulated cellular proliferation | |
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NIH-3T3 cells overexpressing IGF-1 or insulin receptors are plated on 96-well plates (2,000-5,000 cells/well) and maintained overnight in complete medium. Cells are then changed to DMEM containing 1% FBS in the presence of 10 nM IGF-1 or insulin and various concentrations of AG-1024 for 120 hours. Medium is replaced every 48 hours. At the indicated periods of time, the medium is aspirated from the wells and 100 μL MTT is added to each well. The cells are then incubated for 4 hours at 37 °C and lysed by addition of 100 μL isoamylic alcohol and shaking for 20 minutes. The plate is then read in the ELISA reader at 570 and 690 nm. The IC50 value is calculated at the 120-hour time point. | ||
細胞アッセイ | 細胞株 | MCF-7 |
濃度 | Dissolved in DMSO, final concentration 10 μM | |
反応時間 | 24, 48 or 72 hours | |
実験の流れ | Cells are exposed to AG-1024 for 24, 48 or 72 hours. For the determination of proliferation, cells are harvested and counted with trypan blue dye exclusion. Apoptosis is evaluated by dual staining of MCF-7 with fluoresceine anti-digoxigenin and propidium iodide. Briefly, fixed cells are washed with PBS, suspended in TdT buffer with TdT enzyme and Dig-dUTP for 60 minutes, and suspended in FITC blocking solution with anti-Dig-Fluorescein for 30 minutes at room temperature and kept in a dark place. Cells are then rinsed in buffer and resuspended in propidium iodide/RNase A solution for 30 minutes then analyzed by flow cytometry. For the assessment of phospho-Akt1, Bax, p53, bcl-2 and p21, cells are lysed and analyzed by western blot. | |
動物実験 | 動物モデル | Female nude mice implanted subcutaneously with Ba/F3-p210 cells |
投薬量 | 30 μg/day | |
投与方法 | Injected i.p |
Data from [Blood, 2013, 122(9), 1621-33]
Data from [Mol Endocrinol, 2011, 25, 2041-53]
Data from [Data independently produced by , , Mol Psychiatry, 2018, 23(4):833-842]
LTK and ALK promote neuronal polarity and cortical migration by inhibiting IGF1R activity [ EMBO Rep, 2023, 24(7):e56937] | PubMed: 37291945 |
Ras-mutant cancers are sensitive to small molecule inhibition of V-type ATPases in mice [ Nat Biotechnol, 2022, 10.1038/s41587-022-01386-z] | PubMed: 35879364 |
Tyrphostin AG1024 Suppresses Coronaviral Replication by Downregulating JAK1 via an IR/IGF-1R Independent Proteolysis Mediated by Ndfip1/2_NEDD4-like E3 Ligase Itch [ Pharmaceuticals (Basel), 2022, 15(2)241] | PubMed: 35215353 |
Targeting oncogenic mutations in colorectal cancer using cryptotanshinone [ PLoS One, 2021, 16(2):e0247190] | PubMed: 33596259 |
Regulation of Hippo-YAP Signaling by Insulin-Like Growth factor-1 Receptor in the Tumorigenesis of Diffuse Large B-cell Lymphoma [ J Hematol Oncol, 2020, 13(1):77] | PubMed: 32546241 |
Myeloid cells provide critical support for T-ALL in vivo [ The University of Texas at Austin, 2020, ] | PubMed: None |
An Autocrine IL-6/IGF-1R Loop Mediates EMT and Promotes Tumor Growth in Non-small Cell Lung Cancer. [ Int J Biol Sci, 2019, 15(9):1882-1891] | PubMed: 31523190 |
mTORC2-mediated PDHE1α nuclear translocation links EBV-LMP1 reprogrammed glucose metabolism to cancer metastasis in nasopharyngeal carcinoma. [ Oncogene, 2019, 38(24):4669-4684] | PubMed: 30745576 |
A novel 5HT3 receptor–IGF1 mechanism distinct from SSRI-induced antidepressant effects [Kondo M, et al. Mol Psychiatry, 2018, 23(4):833-842] | PubMed: 28439104 |
Insulin-like growth factor binding protein 4 inhibits proliferation of bone marrow mesenchymal stem cells and enhances growth of neurospheres derived from the stem cells [ Cell Biochem Funct, 2018, 36(6):331-341] | PubMed: 30028031 |
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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