AT7519

製品コードS1524

AT7519化学構造

分子量(MW):382.24

AT7519は一種の多種CDK阻害剤で、CDK1、2、4、6と9に作用する時のIC50値が10-210 nMですが、CDK3に作用効果が少し弱くて、CDK7を抑制する活性が殆どありません。臨床2期。

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カスタマーフィードバック(3)

  • Lysates of MDM treated with five-fold dilutions of the indicated compounds (starting concentration: AT7519, 0.5 mmol/l, roscovitine 4 mmol/l) were subjected to SDS-PAGE, transferred, and immunoblotted with antiphopho-SAMHD1, anti-SAMHD1 and anti-Hsp90 antibodies. MDM, monocyte-derived macrophage; SAMHD1, sterile a motif and HD domain-containing protein-1; SD, standard deviation.

    AIDS 2014 28(15), 2213-22. AT7519 purchased from Selleck.

    AT7519 drives eosinophil apoptosis and subsequent clearance by macrophages as assessed by morphological analysis. Representative images from vehicle (E) and AT7519 treated (F) animals are shown (Magnification x400 (i) and x1000 (ii and iii)). In vehicle treated animals (E), black arrows indicate healthy, viable eosinophils while in AT7519-treated animals (F), black arrows indicate typically apoptotic eosinophils and white arrows apoptotic cells inside macrophages.

    PLoS One 2011 6(9), e25683. AT7519 purchased from Selleck.

  • U87MG astroglioma cells were loaded with CFSE (5 μM) and treated with 0-400 nM of AT7519. Data acquired on day 0 and day 3 on a FACS Caliber flow cytometer and analysed by FlowJo. Results indicated that AT7519 partially inhibited cell proliferation. Higher than 400 nM resulted in cell death.

    Dr. Srinivas Narasipura of Rush University Medical Center. AT7519 purchased from Selleck.

製品安全説明書

CDK阻害剤の選択性比較

生物活性

製品説明 AT7519は一種の多種CDK阻害剤で、CDK1、2、4、6と9に作用する時のIC50値が10-210 nMですが、CDK3に作用効果が少し弱くて、CDK7を抑制する活性が殆どありません。臨床2期。
ターゲット
CDK9/CyclinT [1] CDK5/p35 [1] CDK2/CyclinA [1] GSK-3β [1] CDK4/CyclinD1 [1]
<10 nM 13 nM 47 nM 89 nM 100 nM
体外試験

AT7519 is an ATP competitive CDK inhibitor with a Ki value of 38 nM for CDK1. AT7519 is inactive against all non-CDK kinases with the exception of GSK3β (IC50 = 89 nM). AT7519 shows potent antiproliferative activity in a variety of human tumor cell lines with IC50 values ranging from 40 nM for MCF-7 to 940 nM for SW620 consistent with the inhibition of CDK1 and CDK2. [1] AT7519 induces dose-dependent cytotoxicity in multiple myeloma (MM) cell lines with IC50 values ranging from 0.5 to 2 μM at 48 hours, with the most sensitive cell lines being MM.1S (0.5 μM) and U266 (0.5 μM) and the most resistant MM.1R (>2 μM). It does not induce cytotoxicity in peripheral blood mononuclear cells (PBMNC). AT7519 partially overcomes the proliferative advantage conferred by IL6 and IGF-1 as well as the protective effect of bone marrow stromal cells (BMSCs). AT7519 induces rapid dephosphorylation of RNA pol II CTD at serine 2 and serine 5 sites, and leads to the inhibition of transcription, partially contributing to AT7519 induced cytotoxicity of MM cells. AT7519 induces activation of GSK-3β by down-regulating GSK-3β phosphorylation, which also contributes to AT7519 induced apoptosis independent of the inhibition of transcription. [2]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 cells NXXPVJZSS3m2b4TvfIlkyqCjc4PhfS=> M3zwOlczKGh? MnztR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTGNVOTF4IHPlcIx{KGG|c3Xzd4VlKGG|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCDbHHtZZIh[my3ZTDhd5NigSxiSVO1NF0xNjB6IN88US=> MWKyOlEyPTV5MR?=
A2780 cells MYnQdo9tcW[ncnH0bY9vKGG|c3H5 M3jyUVczKGh? NWn2c2ppSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBNlc5OCClZXzsd{Bie3Onc4Pl[EBieyClZXzsJJZq[WKrbHn0fUBi\nSncjC3NkBpenNiYomgZYxidWG{IHLseYUh[XO|YYmsJGlEPTB;MD6zOUDPxE1? MV6xPFY2PjlzMR?=
MRC5 cells NIDNOVFRem:uaX\ldoF1cW:wIHHzd4F6 MWe3NkBp NUDhV4s6SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNVmM2KGOnbHzzJIF{e2W|c3XkJIF{KGOnbHygeoli[mmuaYT5JIFnfGW{IEeyJIhzeyCkeTDhcIFu[XJiYnz1[UBie3OjeTygTWM2OD1yLkm4JO69VQ>? MYqxPFY2PjlzMR?=

多くの細胞株試験データを見る場合、クリックしてください

体内試験 A twice daily dosing of AT7519 (9.1 mg/kg) causes tumor regression of both early-stage and advanced-stage s.c. tumors in the HCT116 and HT29 colon cancer xenograft models. [1] AT7519 treatment (15 mg/kg) inhibits tumor growth and prolongs the median overall survival of mice in the human MM xenograft mouse model in association with increased caspase 3 activation. [2]

お薦めの試験操作(参考用のみ)

キナーゼ試験:[1]
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In vitro Kinase Assays:

Kinase assays for CDK1, CDK2 and GSK3-β are all carried out in a radiometric filter binding format. Assays for CDK5 are in DELFIA format and for CDKs 4 and 6 in ELISA format. For CDKs 1 and 2, the relevant CDK and 0.12 μg/mL Histone H1 are incubated in 20 mM MOPS, pH 7.2, 25 mM β-glycerophosphate, 5 mM EDTA, 15 mM MgCl2, 1 mM sodium orthovanadate, 1 mM DTT, 0.1 mg/mL BSA, 45 μM ATP (0.78 Ci/mmol) and different concentrations of AT7519 for 2 or 4 hours respectively. For GSK3-β, the relevant enzyme and 5 μM glycogen synthase peptide 2 along with 10 mM MOPS pH 7.0, 0.1 mg/mL BSA, 0.001% Brij-35, 0.5% glycerol, 0.2 mM EDTA, 10 mM MgCl2, 0.01% β-mercaptoethanol, 15 μM ATP (2.31 Ci/mmol) and different concentrations of AT7519 are incubated for 3 hours. Assay reactions are stopped by adding an excess of orthophosphoric acid and filtered using Millipore MAPH filter plates. The plates are then washed, scintillant added and radioactivity measured by scintillation counting on a Packard TopCount. For CDK5, CDK5/p35 and 1μM of a biotinylated Histone H1 peptide (Biotin-PKTPKKAKKL) are incubated in 25 mM Tris-HCl, pH 7.5, 2.5 mM MgCl2, 0.025% Brij-35, 0.1 mg/mL BSA, 1 mM DTT, 15 μM ATP and different concentrations of AT7519 for 30 minutes. Assay reactions are stopped using EDTA, transferred to Neutravidin-coated plates and phosphorylated peptide quantified by means of a rabbit phospho-cdk1 substrate polyclonal antibody and DELFIA europium-labelled anti-rabbit IgG secondary antibody using time-resolved fluorescence at λex=335nm, λem=620nm. For CDK 4 and 6 assays, plates are coated with GST- pRb769-921 and blocked with Superblock. CDK4 or 6 is incubated with 15 mM MgCl2, 50 mM HEPES, pH 7.4, 1 mM DTT, 1 mM EGTA, pH 8.0, 0.02% Triton X-100, 2.5% DMSO and different concentrations of AT7519; the reaction is initiated by addition of ATP. After 30 minutes, reactions are stopped by the addition of 0.5 M EDTA pH 8.0. Plates are then washed and incubated for one hour with the primary antibody (anti- p-Rb Serine 780) diluted in Superblock followed by secondary antibody (alkaline phosphatase linked anti-rabbit) for a further hour. Plates are developed using the Attophos system and fluorescence read on a Spectramax Gemini plate reader at excitation 450 nm and emission 580 nm. In all cases, IC50 values are calculated from replicate curves, using GraphPad Prism software.
細胞試験: [2]
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  • 細胞株: MM.1S, MM.1R, RPMI8226, U266, RPMI8266, RPMI-Dox40, OPM1 cells, primary MM cells and PBMNCs
  • 濃度: Dissolved in DMSO at a concentration of 10 mM, final concentrations 0.25-4 μM
  • 反応時間: 24 or 48 hours
  • 実験の流れ: Cells are incubated with different concentrations of AT7519 for 24 or 48 hours at 37 °C. Cell viability is assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrasodium bromide (MTT) dye absorbance. DNA synthesis is measured by tritiated thymidine uptake (3H-TdR). Apoptosis is assessed by using Annexin V/PI staining. The percentage of cells undergoing apoptosis is defined as the sum of early apoptosis (Annexin V-positive cells) and late apoptosis (Annexin V-positive and PI-positive cells
    (参考用のみ)
動物試験:[2]
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  • 動物モデル: Male SCID mice inoculated subcutaneously with MM.1S cells
  • 製剤: Dissolved in 0.9% saline
  • 投薬量: 15 mg/kg/day
  • 投与方法: Dosed i.p.
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 10 mg/mL (26.16 mM)
Water slightly soluble or insoluble
Ethanol slightly soluble or insoluble
体内 順序で溶剤を入れること:
30% propylene glycol, 5% Tween 80, 65% D5W
30 mg/mL

* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。

化学情報

分子量 382.24
化学式

C16H17Cl2N5O2

CAS No. 844442-38-2
保管
in solvent
別名 N/A

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02503709 Recruiting Metastatic Solid Neoplasm|Unresectable Solid Neoplasm National Cancer Institute (NCI) April 2016 Phase 1
NCT01652144 Completed Mantle Cell Lymphoma NCIC Clinical Trials Group|Astex Pharmaceuticals|Canadian Cancer Trials Group August 2012 Phase 2
NCT01627054 Completed Chronic Lymphocytic Leukemia NCIC Clinical Trials Group|Astex Pharmaceuticals|Canadian Cancer Trials Group August 2012 Phase 2
NCT01183949 Completed Multiple Myeloma Astex Pharmaceuticals|Multiple Myeloma Research Consortium November 2010 Phase 1|Phase 2
NCT00390117 Completed Lymphoma|Unspecified Adult Solid Tumor, Protocol Specific NCIC Clinical Trials Group|Canadian Cancer Trials Group August 2006 Phase 1

技術サポート

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

Handling Instructions

他の質問がある場合は、お気軽くお問合せください。

  • * 必須

CDK信号経路図

CDK Inhibitors with Unique Features

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID