Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ipatasertib (GDC-0068) 是选择性的,ATP 竞争性的pan-Akt 抑制剂,能够抑制Akt1 (IC50:5 nM),Akt2 (IC50:18 nM),Akt3 (IC50:8 nM)。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 359 | 现货 | ||
2 mg | ¥ 513 | 现货 | ||
5 mg | ¥ 973 | 现货 | ||
10 mg | ¥ 1,470 | 现货 | ||
25 mg | ¥ 2,550 | 现货 | ||
50 mg | ¥ 3,980 | 现货 | ||
100 mg | ¥ 5,820 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 973 | 现货 |
产品描述 | Ipatasertib (GDC-0068) (GDC-0068), a highly specific pan-Akt inhibitor, targets Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM, respectively. |
靶点活性 | Akt3:8 nM, Akt2:18 nM, Akt1:5 nM |
体外活性 | Testing against a broad panel of 230 kinases, GDC-0068 only inhibits 3 kinases by >70% at 1 μM concentration (PRKG1α, PRKG1β, and p70S6K, with IC50 of 98 nM, 69 nM, and 860 nM, respectively). GDC-0068 displays >100-fold selectivity for Akt over PKA with IC50 of 3.1 μM. In LNCaP, PC3 and BT474M1 cells, GDC-0068 treatment inhibits the phosphorylation of the Akt substrate, PRAS40 with IC50 of 157 nM, 197 nM, and 208 nM, respectively. Furthermore, GDC-0068 selectively inhibits cell cycle progression and viability of cancer cell lines driven by Akt signaling, including those with defects in the tumor suppressor PTEN, oncogenic mutations in PIK3CA, and amplification of HER2, with strongest effects in HER2+ and Luminal subtypes. [1-4] |
体内活性 | Oral administration of GDC-0068 in PC3 prostate tumor xenografts model induces down-regulation of p-PRAS40. In BT474-Tr xenografts, GDC-0068 treatment reduces pS6 and peIF4 g levels, re-localizes FOXO3a to nucleus, and induces feedback upregulation of HER3 and pERK. Administration of GDC-0068 exhibits potent antitumor efficacy in multiple xenograft tumor models, including the PTEN-deficient prostate cancer models LNCaP and PC3, the PIK3CA H1047R mutant breast cancer model KPL-4, and MCF7-neo/HER2 tumor model. [1-4] |
激酶实验 | Kinase Assay: The fluorescence polarization assay for ATP competitive inhibition is done as follows: mPI3Kα dilution solution (90 nM) is prepared in fresh assay buffer (50 mM Hepes pH 7.4, 150 mM NaCl, 5 mM DTT, 0.05% CHAPS) and kept on ice. The enzyme reaction contains 0.5 nM mouse PI3Kα (p110α/p85α complex purified from insect cells), 30 μM PIP2, PF-04691502 (0, 1, 4, and 8 nM), 5 mM MgCl2, and 2-fold serial dilutions of ATP (0–800 μM). Final dimethyl sulfoxide is 2.5%. The reaction is initiated by the addition of ATP and terminated after 30 minutes with 10 mM EDTA. In a detection plate, 15 uL of detector/probe mixture containing 480 nM GST-Grp1PH domain and 12 nM TAMRA tagged fluorescent PIP3 in assay buffer is mixed with 15 uL of kinase reaction mixture. The plate is shaken for 3 minutes, and incubated for 35 to 40 minutes before reading on an LJL Analyst HT. |
细胞实验 | GDC-0068 is prepared in DMSO and stored, and then diluted with appropriate medium before use[2]. The 384-well plates are seeded with 2,000 cells per well in a volume of 54 μL per well followed by incubation at 37°C under 5% CO2 overnight (~16 hours). Compounds (e.g., GDC-0068) are diluted in DMSO to generate the desired stock concentrations then added in a volume of 6 μL per well. All treatments are tested in quadruplicates. After 4 days incubation, relative numbers of viable cells are estimated using CellTiter-Glo and total luminescence is measured on a Wallac Multilabel Reader. The concentration of drug resulting in IC50 is calculated from a 4-parameter curve analysis (XLfit) and is determined from a minimum of 3 experiments. For cell lines that failed to achieve an IC50, the highest concentration tested (10 μM) is listed[2]. |
别名 | GDC-0068, RG7440, 帕他色替 |
分子量 | 458 |
分子式 | C24H32ClN5O2 |
CAS No. | 1001264-89-6 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 85 mg/mL (185.6 mM)
Ethanol: 85 mg/mL (185.6 mM)
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 / Ethanol | 1 mM | 2.1834 mL | 10.917 mL | 21.8341 mL | 54.5852 mL |
5 mM | 0.4367 mL | 2.1834 mL | 4.3668 mL | 10.917 mL | |
10 mM | 0.2183 mL | 1.0917 mL | 2.1834 mL | 5.4585 mL | |
20 mM | 0.1092 mL | 0.5459 mL | 1.0917 mL | 2.7293 mL | |
50 mM | 0.0437 mL | 0.2183 mL | 0.4367 mL | 1.0917 mL | |
100 mM | 0.0218 mL | 0.1092 mL | 0.2183 mL | 0.5459 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。
Ipatasertib 1001264-89-6 Cytoskeletal Signaling PI3K/Akt/mTOR signaling Akt Protein kinase B RG-7440 GDC-0068 RG7440 Inhibitor PKB GDC 0068 inhibit 帕他色替 GDC0068 RG 7440 inhibitor