| 名稱 | PHA-793887 |
| 描述 | PHA-793887 has been used in trials studying the treatment of Advanced/Metastatic Solid Tumors. |
| 細(xì)胞實(shí)驗(yàn) | 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) |
| 激酶實(shí)驗(yàn) | 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. |
| 體外活性 | 20 mg/kg PHA-793887對(duì)攜帶K562和HL60細(xì)胞的移植瘤模型,原代白血病擴(kuò)散細(xì)胞模型和復(fù)發(fā)Philadelphia-陽性急性淋巴性白血病患者高負(fù)荷播散性ALL-2模型有效.PHA-793887（10-30 mg/kg）在人卵巢A2780,結(jié)腸HCT-116和胰腺BX-PC3癌異種移植模型中顯示出良好的功效. |
| 體內(nèi)活性 | PHA-793887誘導(dǎo)細(xì)胞周期停滯,抑制Rb和核磷酸磷酸化,0.2-1 μM時(shí)調(diào)節(jié)細(xì)胞周期蛋白E和cdc6表達(dá),5 μM時(shí)誘導(dǎo)凋亡。PHA-793887對(duì)白血病細(xì)胞系（包括K562,KU812,KCL22和TOM1）具有細(xì)胞毒性,IC50為0.3-7 μM,但對(duì)正常未刺激的外周血單個(gè)核細(xì)胞或CD34 +造血干細(xì)胞沒有細(xì)胞毒性。PHA-793887作用于白血病細(xì)胞系具有高活性,IC50< 0.1 μM。 PHA-793887抑制許多腫瘤細(xì)胞系（包括A2780,HCT-116,COLO-205,C-433,DU-145,A375,PC3,MCF-7和BX-PC3）的細(xì)胞增殖,IC50為88 nM- 3.4 μM。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 67 mg/mL (185.3 mM)
DMSO : 55 mg/mL (152.15 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | Inhibitor | inhibit | Apoptosis | Cyclin dependent kinase | CDK | PHA-793887 |
| 相關(guān)產(chǎn)品 | L-Glutamic acid | Metronidazole | 5-Fluorouracil | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
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