| 中文名称: | LY 303511 | ||||
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| 英文名称: | LY 303511 | ||||
| 别名: | 8-苯基-2-(1-哌嗪基)-4H-1-苯并吡喃-4-酮;LY303511 抑制剂 LY303511;2-(1-Piperazinyl)-8-phenyl-4H-1-benzopyran-4-one | ||||
| CAS No: | 154447-38-8 | 分子式: | C19H18N2O2 | 分子量: | 306.36 |
| CAS No: | 154447-38-8 | ||||
| 分子式: | C19H18N2O2 | ||||
| 分子量: | 306.36 | ||||
基本信息
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产品编号：L10352 |
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产品名称：LY 303511 |
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CAS: |
154447-38-8 |
储存条件 |
粉末 |
-20℃ |
四年 |
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分子式： |
溶于液体 |
-80℃ |
两年 |
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分子量 |
306.36 |
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化学名： |
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Solubility (25°C) |
体外 |
DMSO |
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Ethanol |
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Water |
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体内（现配现用） |
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＜1mg/ml表示微溶或不溶。 |
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普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。 |
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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 |
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生物活性
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产品描述 |
是 LY294002 的一种结构类似物，但 LY303511 不抑制 PI3K。LY303511 可增强 SHEP-1 神经母细胞瘤细胞的TRAIL 敏感性。LY303511 可逆地阻断 MIN6 胰岛瘤细胞中的 K+ 电流 (IC50=64.6±9.1μM)。 |
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靶点/IC50 |
TRAIL |
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体外研究 |
LY303511 is structurally identical to LY294002 except for a substitution of -O for -NH in the morpholine ring, and does not potently inhibit PI3K. Treatment of cells with LY303511 causes an increase in calcein spread similar to levels of LY294002.The ability of LY303511 to increase gap junctional intercellular communication (GJIC) does not occur concomitant with inhibition of phosphorylation of AKT as measured by immunoblotting[1]. LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via H2O2-MAPK activation and up-regulation of death receptors. SHEP-1 cells are exposed to varying concentrations of LY303511 (LY30), TRAIL, and a combination of the two (1 h preincubation with LY303511 followed by TRAIL for 4 hours). SHEP-1 cells are responsive to TRAIL (~10%,~15%, and ~30% reduction in the surviving fraction at 25,50,and 100 ng/mL, respectively); however, treatment with LY303511 (12.5, 25, or 50 μM) has no effect on cell viability.However,incubation of cells with LY303511 (25 μM) for 1 hour followed by 4 hours exposure to 50 ng/mL of TRAIL has a strong synergistic effect (~40% reduction in viable cells with LY303511+TRAIL versus ~15% with TRAIL alone)[2]. LY303511 is a negative control compound with respect to PI3K activity. In MIN6 insulinoma cells, Wortmannin (100 nM) has no effect on whole-cell outward K+currents, but LY294002 and LY303511 reversibly block currents in a dose-dependent manner (IC50=9.0±0.7 μM and 64.6±9.1μM, respectively). Kv2.1 and Kv1.4 are highly expressed in beta-cells, and in Kv2.1-transfected tsA201 cells, 50 μM LY294002 and 100 μM LY303511 reversibly inhibit currents by 99% and 41%,respectively. LY303511 blocks currents with an IC50 of 64.6±9.1µM, with a maximal inhibition of ~90% at 500 µM (n≥5 cells at each concentration). |
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体内研究 |
Intraperitoneal administration of vehicle or LY303511 (10mg/kg/day) is performed when tumors reach a volume of ~150mm 3, at which time 35 mice have developed a tumor. After 21 days, >15% of the mice require euthanasia because of excessive tumor growth, and these data are censored due to unreliable estimates of average tumor volume. The administration of LY303511, 10mg/kg/day, is sufficient to inhibit PC-3 tumor growth in vivo. |
推荐实验方法(仅供参考)
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激酶实验： |
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激酶活性测定 |
通过杆状病毒表达系统纯化人源的VEGFR受体激酶1, 2和3的C端催化活性区域的GST融合蛋白，用这些蛋白在384孔微量滴定板上利用均相时间分辨荧光技术(HTRF)对VEGRF1,2和3的酶活性进行分析。首先将10μL活化的VEGFR2激酶溶液[终浓度为1nM酶溶于0.1M HEPES，pH 7.5,包含0.1mg/mL BSA，300μM DTT]加入10μL底物溶液[终浓度为360 nM多肽（生物素偶联的aminohexyl-EEEEYFELVAKKKK-NH2），75μM ATP, 10μM MgCl2]，同时加入1μL 溶解在DMSO中的Pazopanib。滴定板在室温条件下孵育1小时，然后加入20μL 100mM 的EDTA终止反应。终止之后，加入20μL HTRF试剂（终浓度为15nM 链亲和素偶联的别藻蓝素，用0.1mg/mL BSA, 0.1M HEPES, pH 7.5稀释的1nM铕标记的酪氨酸磷酸化抗体）孵育十分钟以上。使用Wallac Victor的时间分辨荧光仪测定665nM处的荧光值，时间间隔为50μs。 |
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细胞实验: |
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Human neuroblastoma SHEP-1 cells are maintained in DMEM supplemented with 10% fetal bovine serum and 1% Penicillin. In a typical survival assay, SHEP-1 cells (8×104 per well) plated in 24-well plates for 24h are exposed to LY303511 (12.5, 25, and 50μM), TRAIL (25, 50, and 100ng/mL), and a combination of the two (1h preincubation with LY303511 followed by TRAIL for 4h). Cytotoxicity is determined by the crystal violet assay. After drug exposure, cells are washed with PBS and incubated for 20 min with crystal violet solution (200μL). The excess crystal violet solution is washed away with distilled water, and the remaining crystals are dissolved with 20% acetic acid. Viability is determined by absorbance at 595 nm wavelength using an automated ELISA reader. Cell viability experiments are performed similarly with 2,000 units/mL of catalase,4 μM JNK inhibitor SP600125, 10μM p38 inhibitor SB202190, 20 μM MAPK/ERK kinase (MEK) inhibitor PD98059, 50μM of caspase-8 inhibitor Z-IETD-FMK or pan-caspase inhibitor Z-VAD FMK, or death receptor blocking antibodies (4 μg/mL anti-DR4 or 1μg/mL anti-DR5), or in cells transfected with small interfering RNA (siRNA) for silencing JNK and ERK expression, respectively. Cells are preincubated for 1 h with LY303511 and the respective inhibitor or catalase before the addition of TRAIL. Similar sensitizing effect of LY303511 on TRAIL-induced apoptosis is carried out with SY5Y neuroblastoma, T98G glioblastoma, Jurkat leukemia, CEM myelogenous leukemia, HeLa ovarian carcinoma,and HT29 colorectal carcinoma cell lines.
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动物实验: |
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Mice Human prostate adenocarcinoma (PC-3) cells (ATCC CRL-1435) are culture d in vitro before harvesting and implantation of 1×106 cells in 20% Matrigel per athymic NCR nude mouse by subcutaneous injection at the flank. Inoculated mice are subdivided into four groups of 10.Administration of vehicle or LY303511, 10mg/kg/day, is begun(day 1) when tumors reach ~150mm3 (n=35), and tumor volumes are measured for 30 days at the indicated time points. |
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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为：C1V1 = C2V2 ( 输入 输出 )
