化合物PHA-793887 T2113

Product Introduction
Bioactivity


英文名: PHA-793887

描述: PHA-793887 是一种ATP 竞争性的CDK 抑制剂，可抑制 Cdk2、Cdk1、Cdk4 和 Cdk9 的活性，IC50值分别为 8 nM、60 nM、62 nM 和 138 nM，同时可抑制糖原合酶激酶 3β，IC50值为 79 nM。

细胞实验: Cells are seeded into 96- or 384-wells plates at final concentration ranging from 1 × 104 to 3 × 104 per cm2. After 24 hours, cells are treated using serial dilution of PHA-793887. At 72 hours after the treatment, the amount of cells are evaluated using the CellTiter-Glo assay. IC50 values are calculated using a sygmoidal fitt(Only for Reference)

激酶实验: CDK Kinase Assay: The biochemical activity of compounds is determined by incubation with specific enzymes and substrates, followed by quantitation of the phosphorylated product. PHA-793887 (1.5 nM–10 μM) is incubated for 30?90 min at room temperature in the presence of ATP/33P-γ-ATP mix, substrate, and the specific enzyme (0.7?100 nM) in a final volume of 30 μL of kinase buffer, using 96 U bottom plates. After incubation, the reaction is stopped and the phosphorylated substrate is separated from nonincorporated radioactive ATP using SPA beads, Dowex resin, or Multiscreen phosphocellulose filter as follows: (1) For SPA Assays. The reaction is stopped by the addition of 100 μL of PBS + 32 mM EDTA + 0.1% Triton X-100 + 500 μM ATP, containing 1 mg of streptavidin-coated SPA beads. After 20 min of incubation for substrate capture, 100 μL of the reaction mixture is transferred into Optiplate 96-well plates containing 100 μL of 5 M CsCl, left to stand for 4 hours to allow stratification of beads to the top of the plate, and counted using TopCount to measure substrate-incorporated phosphate. (2) For Dowex Resin Assay. An amount of 150 μL of resin/formate, pH 3.00, is added to stop the reaction and capture unreacted 33P-γ-ATP, separating it from the phosphorylated substrate in solution. After 60 min of rest, 50 μL of supernatant is transferred to Optiplate 96-well plates. After the additon of 150 μL of Microscint 40, the radioactivity is counted in the TopCount. (3) For Multiscreen Assay. The reaction is stopped with the addition of 10 μL of EDTA (150 mM). An amount of 100 μL is transferred to a MultiScreen plate to allow substrate binding to phosphocellulose filter. Plates are then washed three times with 100 μL of H2PO4 (75 mM) filtered by a MultiScreen filtration system, and dried. After the additon of 100 μL of Microscint 0, radioactivity is counted in the TopCount. IC50 values are obtained by nonlinear regression analysis.

体外活性: 20 mg/kg PHA-793887对携带K562和HL60细胞的移植瘤模型,原代白血病扩散细胞模型和复发Philadelphia-阳性急性淋巴性白血病患者高负荷播散性ALL-2模型有效.PHA-793887（10-30 mg/kg）在人卵巢A2780,结肠HCT-116和胰腺BX-PC3癌异种移植模型中显示出良好的功效.

体内活性: PHA-793887诱导细胞周期停滞,抑制Rb和核磷酸磷酸化,0.2-1 μM时调节细胞周期蛋白E和cdc6表达,5 μM时诱导凋亡。PHA-793887对白血病细胞系（包括K562,KU812,KCL22和TOM1）具有细胞毒性,IC50为0.3-7 μM,但对正常未刺激的外周血单个核细胞或CD34 +造血干细胞没有细胞毒性。PHA-793887作用于白血病细胞系具有高活性,IC50< 0.1 μM。 PHA-793887抑制许多肿瘤细胞系（包括A2780,HCT-116,COLO-205,C-433,DU-145,A375,PC3,MCF-7和BX-PC3）的细胞增殖,IC50为88 nM- 3.4 μM。

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: Ethanol : 67 mg/mL (185.3 mM)
DMSO : 67 mg/mL (185.3 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)


关键字: Inhibitor | inhibit | Apoptosis | Cyclin dependent kinase | CDK | PHA-793887

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相关库: Drug Repurposing Compound Library | Anti-Cancer Drug Library | Clinical Compound Library | Kinase Inhibitor Library | Inhibitor Library | Anti-Cancer Clinical Compound Library | Anti-Cancer Active Compound Library | Apoptosis Compound Library | NO PAINS Compound Library | Bioactive Compound Library

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