Powder: -20°C for 3 years | In solvent: -80°C for 2 years
Deguelin 是一种 PI3K/Akt 抑制剂,是从 Mundulea sericea 家族植物中分离出来的鱼藤酮类化合物。
产品描述 | Deguelin is a PI3K/AKT Inhibitor, which is a natural product isolated from plants in the Mundulea sericea family. |
体外活性 | In leukaemia cell lines, Deguelin downregulates Akt phosphorylation through activating PI3K/Akt axis. Deguelin increases the sensitivity of human leukaemia cells to chemotherapeutic drugs. In U937 cells deguelin does not affect the expression or the phosphorylation levels of either p44/42 or p38 MAP kinases. Deguelin, when employed for 24 h at 10 nmol/l, causes an S phase arrest of U937 cells, with interference of progression to G2/M phase. While employed alone up to a concentration of 10 nmol/l for 24 h, Deguelin does not significantly increase the apoptotic rate of U937 cells.Deguelin (10 or 100 nmol/l) is potent in inhibiting Akt phosphorylation,while deguelin does not affect total Akt expression. Deguelin dephosphorylates Akt and increases cytarabine sensitivity of AML blasts but not of CB CD34+. |
体内活性 | In pre-clinical trials, deguelin markedly decreased the tumor incidence. It exhibited significant anti-tumorigenesis and anti-proliferative activity in various types of cancer both in vitro and in vivo. Topically-administered deguelin significantly suppressed the multiplicity of skin tumors with UVB-induction, indicating its effect as a potential cancer chemopreventive agent. Treatment with deguelin, a potential mitochondria complex I inhibitor, reduced tyrosine hydroxylase-positive neurons, leading to Parkinson's disease.Deguelin promoted a PD-like syndrome, mainly by Src/STAT signaling, since α-synuclein (a key protein function in the pathogenesis of PD) was phosphorylated by deguelin-activated Src.Deguelin inhibits in vivo angiogenesis of chick chorioallantoic membrane (CAM) without cytotoxic effect and significantly reduces laser-induced CNV in a mouse model of AMD without significant retinal toxicity. In A/J mice, deguelin clearly reduced the tumor multiplicity and volume, as well as the overall tumor burden with exposure to the tobacco-specific carcinogen benzo(a)pyrene (Bap) and other carcinogens, with no detectable toxicity. |
激酶实验 | Caspase 3 activity is determined using Caspase-Glo-3 assays. This assay provides luminogenic substrate in a buffer system optimized for each specific caspase activity. The caspase cleavage of the substrate is followed by generation of a luminescent signal. The signal generated is proportional to the amount of caspase activity present in the sample. Protein (10 μg) from the cell samples is diluted in water to a final volume of 50 μL and added to a white 96-well microtitre plate, followed by 50 μL of Caspase-Glo-3 reagent. The plate is sealed and gently mixed at 300-500 rpm for 30 s and incubated at room temperature for 30 min. Luminescence is measured in a microplate reader (TECAN Infinite 200). |
细胞实验 | U937 Cells are incubated with the indicated concentrations (1 nM, 10 nM, 100 nM) of deguelin for 24 h.Flow cytometric analysis of cell cycle in response to deguelin. Flow cytometric analysis of cell cycle in response to deguelin. |
动物实验 | A/J mice were treated by oral gavage of 5.0 or 10.0 mg/kg deguelin dissolved in corn oil. |
别名 | (-)-cis-Deguelin, 鱼藤素, (-)-Deguelin, 魚藤素 |
分子量 | 394.42 |
分子式 | C23H22O6 |
CAS No. | 522-17-8 |
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
Ethanol: 19.7 mg/mL (50 mM)
DMSO: 39.4 mg/mL (100 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
参数 | 值 | 评价 | |
结构信息 | |||
氢键受体数 | 6 | Excellent | |
可旋转键的数量 | 2 | Excellent | |
环数 | 5 | Excellent | |
最大环中的原子数 | 22 | ― | |
杂原子数 | 6 | Excellent | |
稳定性 | |||
刚性键数 | 27 | Excellent | |
柔性 | 0.074 | ― | |
立体中心数 | 2 | Excellent | |
溶解性 | |||
拓扑极性表面积 | 63.22 | Excellent | |
水溶性值的对数 | -4.590 log mol/L | ― | |
正辛醇/水分配系数的对数 | 4.573 log mol/L | ― | |
pH=7.4时正辛醇/水分布系数的对数 | 4.055 log mol/L | ― | |
药代动力学参数 | |||
定量评估药物相似性 | 0.767 | Excellent | |
合成可行性分数 | 3.698 | Excellent | |
化合物和天然产物在化学空间中的接近度评分 | 2.264 | ― | |
类药五原则 | Accepted | Accepted | |
葛兰素史克内使用的成分 ADMET 分析规则 | Rejected | Rejected | |
Golden Triangle | Accepted | Accepted | |
吸收 | |||
人结肠癌的Caco-2细胞渗透性 | -4.906 | Excellent | |
Madin-Darby 犬肾细胞渗透性 | 0.0000322141 cm/s | Excellent | |
Pgp抑制剂 | 0.999 | Poor | |
Pgp底物 | 0 | Excellent | |
人体肠道吸收性 | 0.006 | Excellent | |
人体口服生物利用度20% | 0.008 | Excellent | |
分布 | |||
血浆蛋白结合率 | 0.9827 | ― | |
体积分布 | 0.74 | Excellent | |
血脑屏障通透性 | 0.115 | Excellent | |
血浆中未结合的部分 | 0.054 | Medium | |
代谢 | |||
CYP 1A2 抑制剂 | 0.297 | ― | |
CYP 2C19 抑制剂 | 0.897 | ― | |
CYP 2C9 抑制剂 | 0.882 | ― | |
CYP 2D6 抑制剂 | 0.937 | ― | |
CYP 3A4 抑制剂 | 0.949 | ― | |
CYP 1A2 底物 | 0.858 | ― | |
CYP 2C19 底物 | 0.851 | ― | |
CYP 2C9 底物 | 0.902 | ― | |
CYP 2D6 底物 | 0.849 | ― | |
CYP 3A4 底物 | 0.646 | ― | |
排泄 | |||
药物的清除 | 5.186 | Medium | |
药物的半衰期 | 0.093 | Excellent | |
毒性参数 | |||
Pfizer Rule | Rejected | Rejected | |
SR-MMP | 0.888 | ― | |
致毒剂量 | |||
FDA 推荐的每日最大剂量 | 0.847 | Poor | |
IGC50 | 4.826 | ― | |
LC50FM | 7.251 | ― | |
LC50DM | 7.069 | ― | |
致畸性 | |||
NR-AR(Androgen receptor) | 0.016 | Excellent | |
NR-AR-LBD(Androgen receptor) | 0.143 | Excellent | |
NR-Aromatase | 0.847 | Poor | |
NR-ER(Estrogen receptor) | 0.376 | Medium | |
NR-ER-LBD(Estrogen receptor) | 0.759 | Poor | |
致敏性 | |||
皮肤致敏规则 | 3 | ― | |
皮肤致敏 | 0.167 | Excellent | |
急性毒性 | |||
大鼠经口急性毒性 | 0.696 | Medium | |
器官毒性 | |||
hERG 阻滞剂 | 0.11 | Excellent | |
人体肝毒性 | 0.842 | Poor | |
药物性肝损伤 | 0.735 | Poor | |
直接刺激性 | |||
眼睛刺激性 | 0.003 | Excellent | |
眼睛腐蚀性 | 0.04 | Excellent | |
呼吸道毒性 | 0.857 | Poor | |
致突变性 | |||
污染物致突变性 | 0.222 | Excellent | |
致肿瘤性 | |||
致癌性 | 0.767 | Poor | |
抗氧化反应元件 | 0.819 | Poor | |
ATP酶家族含AAA结构域蛋白5 | 0.805 | Poor | |
SR-p53 | 0.959 | Poor |
中药材名称 | 中药材拉丁名 | 性 | 味 | 归经 |
灰叶根 | Tephrosia purpurea(L.)Pers. | 凉 | 微苦 | 脾, 胃 |
铃兰 | Convallaria keiskei Miq. | 温 | 甘, 苦 | |
毛鱼藤 | Derris elliptica (Roxb.) Benth. | - | ― | |
木榄 | Bruguiera gymnorhiza (Linnaeus) Savigny | 平 | 涩 | 大肠 |
鱼藤 | Derris trifoliata | 温 | 苦, 辛 | 肝 |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
bottom
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Deguelin 522-17-8 Apoptosis Autophagy Cytoskeletal Signaling PI3K/Akt/mTOR signaling Akt PI3K inhibit (-)-cis-Deguelin Protein kinase B 鱼藤素 PKB Inhibitor (-)-Deguelin 魚藤素 inhibitor