Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Pictilisib (GDC-0941) 是一种PI3Kα/δ抑制剂,IC50为 3 nM。它对110β和 p110γ 具有适度的选择性,分别为11倍和25倍。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
5 mg | ¥ 531 | 现货 | ||
10 mg | ¥ 697 | 现货 | ||
50 mg | ¥ 1,698 | 现货 | ||
100 mg | ¥ 2,683 | 现货 | ||
200 mg | ¥ 3,775 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 598 | 现货 |
产品描述 | Pictilisib (GDC-0941) (GDC-0941) is a potent pan inhibitor of class I catalytic subunits of PI3K (IC50s: 3/33/3/75 nM for p110α/β/δ/γ). |
靶点活性 | p110β:33 nM (cell free), p110δ:3 nM (cell free), p110α:3 nM (cell free) |
体外活性 | Pictilisib是这些细胞系中细胞增殖的强效抑制剂,具有亚μM级的IC50。在U87MG、PC3和MDA-MB-361细胞中观察到对Akt (Ser473) 磷酸化的强效抑制,其IC50分别为46、37和28 nM [1]。与单一化合物治疗相比,Pictilisib和多西他赛联合使用在体外测试的乳腺癌细胞系中减少了80%以上的肿瘤细胞存活率。在MDA-MB-453细胞系中计算出的Bliss和为0,表明了添加效应的组合效果,而其他肿瘤细胞系计算出的Bliss和>0,表明了协同效应 [2]。使用250 nM Pictilisib处理2小时,在所有测试的细胞系中pAKT的抑制率为40%-85%。Pictilisib通过剂量依赖性降低细胞增殖/存活率来抑制PI3K/AKT途径。Pictilisib抑制了曲妥珠单抗敏感和不敏感细胞的生长。Pictilisib的IC50值在150到950 nM之间,与曲妥珠单抗的敏感性无关 [3]。 |
体内活性 | 给携带MCF7-neo/HER2乳腺癌异种移植瘤的动物以7.5 mg/kg 的docetaxel或150 mg/kg的Pictilisib治疗,分别导致肿瘤生长延迟和肿瘤停滞。100 mg/kg的Pictilisib与docetaxel的联合使用在治疗期间导致肿瘤停滞,并在停药后持续维持[2]。AZD8055 (20mg/kg)或Pictilisib (75mg/kg)的给药引起血糖水平的短暂上升。无论是AZD8055还是Pictilisib的治疗均显著抑制了Akt的活性及其Thr308和Ser473的磷酸化。AZD8055或GDC-941还抑制了Akt底物PRAS40和Foxo-1/3a的磷酸化[4]。 |
激酶实验 | Recombinant human PI3Kα, PI3Kβ, and PI3Kδ are coexpressed in a Sf9 baculovirus system with the p85α regulatory subunit and purified as GST-fusion proteins using affinity chromatography on glutathione-sepharose. Recombinant human PI3Kγ is expressed as monomeric GST-fusions and purified similarly. GDC-0941 is dissolved in DMSO and added to 20 mM Tris-HCl (pH 7.5) containing 200 μg yttrium silicate (Ysi) polylysine SPA beads, 4 mM MgCl2, 1 mM dithiothreitol (DTT), 1 μM ATP, 0.125 μCi [γ-33P]-ATP, and 4% (v/v) DMSO in a total volume of 50 μL. The recombinant GST-fusion of PI3Kα (5 ng), PI3Kβ (5 ng), PI3Kδ (5 ng), or PI3Kγ (5 ng) is added to the assay mixture to initiate the kinase reaction. After incubation for 1 hour at room temperature, the kinase reaction is terminated with 150 μL PBS. The mixture is then centrifuged for 2 minutes at 2000 rpm and read using a Wallac Microbeta counter. The reported IC50 values are calculated using a sigmoidal, dose-response curve fit in MDL Assay Explorer [1]. |
细胞实验 | All drug treatments were tested in quadruplicate during a 4-day incubation period, and the relative number of viable cells was estimated using CellTiter-Glo. Total luminescence was measured on a Wallac Multilabel Reader. Cells were treated simultaneously with docetaxel (dose range = 0.0003–0.020 μmol/L) or GDC-0941 (dose range = 0.083–5 μmol/L) in an 8 × 10 matrix of concentrations chosen to encompass clinically relevant doses (24). The concentration of drug resulting in EC50 was determined using Prism software. Combination synergy of GDC-0941 and docetaxel was determined by Bliss independence analyses. A Bliss expectation for a combined response (C) was calculated by the equation: C = (A + B) ? (A × B) where A and B are the fractional growth inhibitions of drug A and B at a given dose. The difference between the Bliss expectation and the observed growth inhibition of the combination of drugs A and B at the same dose is the 'Delta.Bliss.' Delta.Bliss scores were summed across the dose matrix to generate a Bliss sum. Bliss sum = 0 indicates that the combination treatment is additive (as expected for independent pathway effects); Bliss sum > 0 indicates activity greater than additive (synergy); and Bliss sum < 0 indicates the combination is less than additive (antagonism). Statistical analysis comparing the Bliss sums for each cell line was conducted by the Student t-test [2]. |
动物实验 | Female nu/nu mice were inoculated subcutaneously with MCF7-neo/HER2 or MX-1 breast cancer cells. When tumors reached a mean volume of 200 to 250 mm3, animals were size-matched and distributed into groups consisting of 10 animals per group. Docetaxel formulated in 3% EtOH, 97% saline was administered intravenously once weekly. GDC-0941, formulated in MCT (0.5% methylcellulose, 0.2% Tween-80) was dosed orally and daily. MAXF1162 is a HER2+/ER+/PR+ patient-derived breast cancer tumor xenograft model established by directly implanting tumors subcutaneously from patient to NMRI nu/nu mice. Tumor volume was calculated as follows: tumor size (mm3) = (longer measurement × shorter measurement2) × 0.5. Tumor sizes were recorded twice weekly over the course of a study. Following data analysis, P values were determined using the Dunnett t test. For pharmacodynamic studies, tumor samples (n = 4) were immediately frozen or fixed in 10% neutral-buffered formalin. Tumors were dissociated in cell extraction buffer, and lysates were analyzed by Western blotting as described above. Immunohistochemistry was conducted using 5-μm paraffin sections of formalin-fixed tissue on a Ventana Benchmark XT instrument by deparaffinization, treatment with antigen retrieval buffer, and incubation with anti-cleaved caspase-3 primary antibody at 37°C. Bound antibody was detected using DABMap technology, and sections were counterstained with hematoxylin [2]. |
别名 | RG7321, GDC-0941 |
分子量 | 513.64 |
分子式 | C23H27N7O3S2 |
CAS No. | 957054-30-7 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 41 mg/mL (79.8 mM)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
H2O: < 1 mg/mL (insoluble or slightly soluble)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 1.9469 mL | 9.7344 mL | 19.4689 mL | 48.6722 mL |
5 mM | 0.3894 mL | 1.9469 mL | 3.8938 mL | 9.7344 mL | |
10 mM | 0.1947 mL | 0.9734 mL | 1.9469 mL | 4.8672 mL | |
20 mM | 0.0973 mL | 0.4867 mL | 0.9734 mL | 2.4336 mL | |
50 mM | 0.0389 mL | 0.1947 mL | 0.3894 mL | 0.9734 mL |
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。
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。
Pictilisib 957054-30-7 Apoptosis Autophagy PI3K/Akt/mTOR signaling PI3K Inhibitor inhibit Phosphoinositide 3-kinase RG7321 RG 7321 GDC 0941 GDC-0941 GDC0941 RG-7321 inhibitor