化合物PD0166285 T6931

Product Introduction
Bioactivity


英文名: PD0166285

描述: PD0166285是 P-gp 的底物，是一种有效的 Wee1 和 Chk1 抑制剂弱抑制。

细胞实验: B16 cells (1 × 105 cells in 100 mm-dishes) are maintained in medium overnight. In addition, the cells are treated with (0, 0.5, 1.0, or 2.0 μM) PD0166285 (including DMSO vehicle) for indicated times. The cells are washed twice with phosphate-buffered saline (PBS). Next, the cells are trypsinized, so the cell numbers in each dish are determined by using a computed cell-counter (Sysmex CDA-500) according to manufacturer's recommendation. (Only for Reference)

激酶实验: Wee1 Mass Screening: Wee1 mass screening is performed using Amersham's p34cdc2 kinase SPA kit with some modifications. Briefly, 45–60 nM full-length Wee1 kinase is incubated with 25 μM compounds, 20 μM ATP, and 122–441 nM Cdc2/cyclin B in a final volume of 50 μl of enzyme dilution buffer [50 mM Tris (pH 8.0), 10 mM NaCl, 10 mM MgCl2, 1 mM DTT, and 0.1 mM Na3VO4]. After 30 min incubation at 30°C, 30 μl of [33P]ATP containing kinase buffer [67 mM Tris (pH 8.0), 40 mM NaCl, 13 mM MgCl2, 1 mM DTT, and 0.13 mM Na3VO4] containing 1 μM biotinylated peptide, and 0.25 μCi of [γ-33P]ATP is added to the reaction and incubated for another 30 min at 30°C. The reaction is stopped by adding 200 μl of stop buffer [50 μM ATP, 5 mM EDTA, 0.1% Triton X-100, and 1.25 mg/ml SPA beads in PBS]. After centrifugation at 2400 rpm for 15 min, the plate is counted with Wallac's Microbeta counter.

动物实验: E98 tumor fragments (8 mm3) were grafted subcutaneously in the flank of Balb/C nude mice (n = 10). For the experiments with the orthotopic tumors, U251 mg and E98 cells were transduced to express Fluc and mCherry, to generate U251-FM and E98-FM cells. One million cells were injected intracranially. Starting at 12 days after tumor inoculation, mice received the WEE1 inhibitor PD0166285 via intraperitoneal injections (500 μl of a 20 μM solution diluted in NaCl) or vehicle for 5 consecutive days. On days 10–15, mice were irradiated with a single dose of irradiation.

体外活性: PD0166285 is identified to inhibit Wee1 activity at nanomolar concentrations. The inhibitor abrogates G2/M checkpoint inducing early cell division. At the cellular level, 0.5 μM PD0166285 dramatically inhibits irradiation-induced Cdc2 phosphorylation at the Tyr-15 and Thr-14 in seven of seven cancer cell lines tested. This G2 checkpoint abrogation by PD0166285 is demonstrated to kill cancer cells. PD0166285 does not inhibit Cdc2/cyclin B but inhibits Chk1 kinase at a much higher concentration (3433 nM). the treatment of cells with the inhibitor is related to microtubule stabilization and decrease in cyclin D transcription. Thus, PD0166285 may be a potentially useful anti-cancer therapy[1][2].

体内活性: PD0166285在0.5 μM浓度下，能够抑制所有测试细胞系中的Cdc2Y15/T14磷酸化，这一效果与细胞的p53状态无关[1]。此外，通过药理学上靶向WEE1的PD0166285能够增强U251-FM GBM肿瘤对体内IR的敏感性[3]。

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

溶解度: Ethanol : 93 mg/mL (181.5 mM)
DMSO : 93 mg/mL (181.5 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)


关键字: PD 166285 | Wee1 | Inhibitor | inhibit | PD0166285 | Apoptosis | PD166285 | PD-0166285 | PD 0166285

相关产品: 1,4-Dideoxy-1,4-epithio-D-ribitol | Xanthohumol | Clofarabine | Concanavalin A | β-Carotene | PD173074 | Isolongifolene | Onatasertib | Ripretinib | Cedrelone

相关库: Anti-Aging Compound Library | Cell Cycle Compound Library | Anti-Cancer Compound Library | Bioactive Compounds Library Max | Inhibitor Library | Kinase Inhibitor Library | Apoptosis Compound Library | Target-Focused Phenotypic Screening Library | NO PAINS Compound Library | Bioactive Compound Library

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