化合物PLX4720 T2473

Product Introduction
Bioactivity


英文名: PLX-4720

描述: PLX-4720 是一种有效且选择性的 B-Raf (V600E) 抑制剂，IC50为 13 nM，与 c-Raf-1（Y340D 和 Y341D 突变）同样有效。

细胞实验: Cells are treated with various concentrations PLX-4720 for 24, 48, and 72 hours. Cell proliferation is measured by using the CellTiter-Glo Luminescent Cell Viability Assay or MTT assay. For cell cycle analysis, supernatant and cells are collected, pelleted, and fixed with 70% ethanol. Before staining with propidium iodide (10 μg/mL), cells are incubated for 1 hour at 37 °C in 0.5 mg/mL RNase I to rid samples of residual RNA contamination. Samples are then analyzed by using the EPICS XL apparatus. For the assessment of apoptosis, media and cells are harvested and pelleted before staining with annexin-FITC and propidium iodide. Samples are subsequently analyzed by using the EPICS XL apparatus [1].

激酶实验: In vitro Raf kinase activities: The in vitro kinase activities of wild type Raf and mutants are determined by measuring phosphorylation of biotinylated-MEK protein using Perkin-Elmer's AlphaScreen Technology. For each enzyme (0.1 ng), 20-μL reactions are carried out in 20 mM Hepes (pH 7.0), 10 mM MgCl2, 1 mM DTT, 0.01% Tween-20, 100 nM biotin-MEK protein, various ATP concentrations, and increasing concentrations of PLX-4720 at room temperature. Reactions are stopped at 2, 5, 8, 10, 20, and 30 minutes with 5 μL of a solution containing 20 mM Hepes (pH 7.0), 200 mM NaCl, 80 mM EDTA, and 0.3% BSA. The stop solution also includes phospho-MEK Antibody, Streptavidin-coated Donor beads and Protein A Acceptor beads. The antibody and beads are preincubated in stop solution in the dark at room temperature for 30 minutes. The final dilution of antibody is 1/2,000, and the final concentration of each bead is 10 μg/mL. The assay plates are incubated at room temperature for one hour then are read on a PerkinElmer AlphaQuest reader [1].

动物实验: Female athymic mice (NCr nu/nu) were implanted s.c. on day 0 with 30–60 mg COLO205 tumor fragments. Treatments began on day 11, when the mean estimated tumor mass was 104 mg (range, 95–113 mg). All animals were dosed with vehicle (5% DMSO, 1% methylcellulose) or PLX4720 suspended in vehicle by gavage daily for 14 consecutive days. Tumor burden (mg) was estimated from caliper measurements [1].

体外活性: PLX4720 inhibits B-Raf(V600E) with an IC50 of 13 nM. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf(V600E)-bearing tumor cell lines but not in cells lacking oncogenic B-Raf [1]. PLX4720 treatment significantly increased BIM expression in the PTEN+ (>14-fold) compared with the PTEN- cell lines (four-fold). Dual treatment of PTEN- cells with PLX4720 and a PI3K inhibitor enhanced BIM expression at both the mRNA and protein level and increased the level of apoptosis through a mechanism involving AKT3 and the activation of FOXO3a [2].

体内活性: In B-Raf(V600E)-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity [1]. In vivo, PLX4720 treatment of 8505c orthotopic thyroid tumors inhibited tumor aggressiveness and significantly upregulated the thyroid differentiation markers thyroid transcription factor 1 and paired box gene 8 [3]. Treatment of orthotopic thyroid tumors, initiated 1 week after tumor cell implantation with PLX4720 caused a significant tumor growth delay and decreased distant metastases, without evidence of toxicity [4].

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

溶解度: Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 77 mg/mL (186.1 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)


关键字: Inhibitor | inhibit | PLX-4720 | Raf kinases | Raf | PLX 4720

相关产品: GSK1904529A | GNE-9815 | LXH254 | GW 5074 | Regorafenib Hydrochloride | Exarafenib | Effusanin A | Griffipavixanthone | K-Ras-IN-1 | Zabofloxacin hydrochloride

相关库: Anti-Neurodegenerative Disease Compound Library | Anti-Liver Cancer Compound Library | Anti-Cancer Compound Library | Fluorochemical Library | Kinase Inhibitor Library | Inhibitor Library | Tyrosine Kinase Inhibitor Library | Anti-Cancer Active Compound Library | Apoptosis Compound Library | MAPK Inhibitor Library

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