AG-490

製品コードS1143 バッチS114301

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 59 mg/mL (200.47 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）
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 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, this compound (5 μM) almost completely blocks the growth of all ALL cells by inducing programmed cell death, with no deleterious effect on normal hematopoiesis. This chemical does not inhibit the activities of Lck, Lyn, Btk, Syk, and Src. [2] It (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] This compound 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] It significantly inhibits the constitutive activation of Stat3 in MOPC, MPC11, and S194 cells, leading to dramatic dose-dependent apoptosis. [6] This chemical (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. It (50 μM) can induce apoptosis of BaF3 cells expressing T315I and E255K mutants of Bcr-Abl. [7] This compound at 30 μM inhibits not only Epo-induced phosphorylation of wild-type JAK2 but also constitutive phosphorylation of the JAK2 V617F mutant. It 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 this compound 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, treatment with this chemical 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 this agent 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 this compound (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 this chemical (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

参考

  • https://pubmed.ncbi.nlm.nih.gov/1676428/
  • https://pubmed.ncbi.nlm.nih.gov/8628398/
  • https://pubmed.ncbi.nlm.nih.gov/9192639/
  • https://pubmed.ncbi.nlm.nih.gov/10380915/
  • https://pubmed.ncbi.nlm.nih.gov/11264165/
  • https://pubmed.ncbi.nlm.nih.gov/12481410/
  • https://pubmed.ncbi.nlm.nih.gov/16818614/
  • https://pubmed.ncbi.nlm.nih.gov/19327411/

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：

Verapamil attenuates myocardial ischemia/reperfusion injury by inhibiting apoptosis via activating the JAK2/STAT3 signaling pathway [ Biomed Pharmacother, 2024, 180:117568] PubMed: 39405898
Mcam stabilizes a luminal progenitor-like breast cancer cell state via Ck2 control and Src/Akt/Stat3 attenuation [ NPJ Breast Cancer, 2024, 10(1):80] PubMed: 39277578
PKM2-mediated STAT3 phosphorylation promotes acute liver failure via regulating NLRP3-dependent pyroptosis [ Commun Biol, 2024, 7(1):1694] PubMed: 39722076
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
S100A8-Mediated Inflammatory Signaling Drives Colorectal Cancer Progression via the CXCL5/CXCR2 Axis [ J Cancer, 2024, 15(11):3452-3465] PubMed: 38817853
Mcam stabilizes luminal progenitor breast cancer phenotypes via Ck2 control and Src/Akt/Stat3 attenuation [ bioRxiv, 2024, 2023.05.10.540211] PubMed: 38562809
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

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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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