AG-490

製品コードS1143 バッチS114303

印刷

化学情報

Chemical Structure Synonyms Tyrphostin B42, Zinc02557947 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H14N2O3
分子量 294.30 CAS No. 133550-30-8
Solubility (25°C)* 体外 DMSO 58 mg/mL (197.07 mM)
Ethanol 6 mg/mL (20.38 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
2.9mg/ml Taking the 1 mL working solution as an example, add 50 μL of 58 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 AG-490 is an inhibitor of EGFR with IC50 of 0.1 μM in cell-free assays, 135-fold more selective for EGFR versus ErbB2, also inhibits JAK2 with no activity to Lck, Lyn, Btk, Syk and Src.
in vitro AG-490 inhibits HER-2 driven cell proliferation with IC50 of 3.5 μM. [1] Corresponding to the specific dose-dependent inhibition of constitutively activated JAK2 in pre-B acute leukemia (ALL) cells, AG-490 (5 μM) almost completely blocks the growth of all ALL cells by inducing programmed cell death, with no deleterious effect on normal hematopoiesis. AG-490 does not inhibit the activities of Lck, Lyn, Btk, Syk, and Src. [2] AG-490 (60-100 μM) blocks the constitutive activation of Stat3sm, and inhibits spontaneous as well as interleukin 2-induced growth of mycosis fungoides (MF) tumor cells with IC50 values of 75 μM and 20 μM, respectively. [3] AG-490 potently inhibits IL-2-mediated human T cell growth with an IC50 of 25 μM by blocking the activities of JAK3 and STAT5a/b. [4] Although AG-490 alone has no effect on proliferation of FDrv210H cells at a concentration of 5 μM, AG-490 can synergize with STI571 to enhance its inhibitory effect on p210bcr-abl driven proliferation. [5] AG-490 significantly inhibits the constitutive activation of Stat3 in MOPC, MPC11, and S194 cells, leading to dramatic dose-dependent apoptosis. [6] AG-490 (100 μM) inhibits Akt phosphorylation, inhibits the activation of nuclear factor-κB, and causes the activation of GSK-3β, leading to the reduction of c-Myc. AG-490 (50 μM) can induce apoptosis of imatinib-resistant BaF3 cells expressing T315I and E255K mutants of Bcr-Abl. [7] AG-490 at 30 μM inhibits not only Epo-induced phosphorylation of wild-type JAK2 but also constitutive phosphorylation of the JAK2 V617F mutant. AG-490 also potently inhibits cytokine-independent cell growth induced by the JAK2 V617F mutant in BaF3 cells. [8]
in vivo Administration of AG-490 drastically reduces the numbers of CD45+ and HLA-DR+ cells from 48 % and 46% in bone marrow of untreated mice, as well as 38% and 22% in the spleen of untreated mice to undetectale levels. [2] In vivo administration of AG-490 causes murine myeloma tumor cell apoptosis but does not inhibit IL-12-mediated macrophage activation and IFN-γ production by lymphocytes. [6] Consistent with the in vitro blocking of JAK2 V617F mutant activity, AG-490 treatment at 0.5 mg/day for 10 days effectively inhibits JAK2 V617F mutant-induced tumorigenesis and tumor cell invasion in nude mice. [8] Combined therapy with AG-490 and IL-12 induces greater antitumor effects than either agent alone in a murine myeloma tumor model. [6]

プロトコル(参考用のみ)

キナーゼアッセイ In vitro kinase autophosphorylation
AG-490 is dissolved in DMSO 10%-H2O-ethanol 45%. Crude membrane extracts (0.125 μg/mL) are preactivated with EGF (20 nM) in 50 mM HEPES buffer, pH 7.6, and 125 mM NaCl, for 15 minutes at 4 °C. Autophosphorylation activity of EGFR or ErbB2 kinase is assayed at 4 °C for 30 seconds in V-shaped 96-well plates. Membrane extracts (8 μL) are added to each well containing reaction mixture (12 μL, 50mM, HEPES, pH 7.4,125 mM NaCl, 12 mM M8Ac2, 2 mM MnCl2, 1 mM NaVO3, 1 μM ATP, and 1 μCi[γ-32P]ATP, final concentrations) and increasing concentrations of AG-490 (4 μL). After termination by addition of hot sample buffer, the samples are run on a 6% SDS-polyacrylamide gel electrophoresis minigel, the gels dried, and autoradiography performed during the linear exposure time period. The receptor bands are scanned densitrometrically, and the results analyzed by the Ez-Fit program. For the analysis of autophosphorylation of JAK2, JAK2 is immunoprecipitated by using anti-JAK2 antibody from lysates of G2 cells pretreated for 16 hours with increasing concentrations of AG-490 (0-50 μM). Immune complexes are then immunoblotted with anti-phosphotyrosine antibody. A dose-dependent inhibition of in vitro kinase activity is demonstrated by assessing JAK2 autophosphorylation.
細胞アッセイ 細胞株 Pre-B ALL
濃度 Dissolved in DMSO, final concentrations ~ 50 μM
反応時間 16 hours
実験の流れ

Cells are exposed to different concentrations of AG-490 for 16 hours. For the determination of cell proliferation, [3H]tymidine (1 μCi) is added 6 hours or more before the cultures are terminated. Cells are then collected and samples counted in a liquid scintillation counter.
動物実験 動物モデル SCID mice intravenously injected with ALL cells
投薬量 0.85 mg + 0.5 mg daily
投与方法 Continuous pump infusion supplemented with daily intraperitoneal injections

カスタマーフィードバック

Data from [Data independently produced by Carcinogenesis, 2013, 34, 1994-9]

Data from [Data independently produced by Carcinogenesis, 2013, 34, 1994-9]

Data from [Prostate, 2013, 73(3), 267-77]

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：

Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell-based vaccine efficiency to elicit antitumor immune response in vitro [ Cytotherapy, 2024, 26(2):145-156] PubMed: 38099895
Kynurenic acid blunts A1 astrocyte activation against neurodegeneration in HIV-associated neurocognitive disorders [ J Neuroinflammation, 2023, 20(1):87] PubMed: 36997969
Syndecan-1 shedding destroys epithelial adherens junctions through STAT3 after renal ischemia/reperfusion injury [ iScience, 2023, 26(11):108211] PubMed: 37942007
Leptin Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells through the Cooperative Action of MAPK/ERK1/2, JAK2/STAT3 and PI3K/AKT Signaling Pathways [ Int J Mol Sci, 2023, 10.3390/ijms242015151] PubMed: 37894835
Induced expression modes of genes related to Toll, Imd, and JAK/STAT signaling pathway-mediated immune response in Spodoptera frugiperda infected with Beauveria bassiana [ Front Physiol, 2023, 14:1249662] PubMed: 37693000
Induced expression modes of genes related to Toll, Imd, and JAK/STAT signaling pathway-mediated immune response in Spodoptera frugiperda infected with Beauveria bassiana [ Front Physiol, 2023, 10.3389/fphys.2023.1249662] PubMed: 37693000
Vagus nerve stimulation protects against cerebral injury after cardiopulmonary resuscitation by inhibiting inflammation through the TLR4/NF-κB and α7nAChR/JAK2 signaling pathways [ World J Emerg Med, 2023, 10.5847/wjem.j.1920-8642.2023.102] PubMed: 37969224
PERK reprograms hematopoietic progenitor cells to direct tumor-promoting myelopoiesis in the spleen [ J Exp Med, 2022, 219(4)e20211498] PubMed: 35266960
Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth [ Cancer Lett, 2022, 544:215812] PubMed: 35780928
Sphingosine-1 phosphate receptor 1 contributes to central sensitization in recurrent nitroglycerin-induced chronic migraine model [ J Headache Pain, 2022, 23(1):25] PubMed: 35144528

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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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